1.Chemical constituents of Incarvillea younghusbandii.
Yu FU ; Yang BAI ; Zhuoma DAWA ; Bingru BAI ; Lisheng DING
China Journal of Chinese Materia Medica 2010;35(1):58-62
OBJECTIVETo study the chemical constituents of Incarvillea younghusbandii.
METHODThe chemical constituents were isolated by various column chromatographic methods and structurally identified by NMR and MS evidence.
RESULTFifteen compounds were obtained and identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), boschniakinic acid (11), tert-O-beta-D-glucopyranosyl-(R)-heraclenol (12), 5-methoxy-8-O-beta-D-glucopyranosyloxypsoralen (13), 1'-O-beta-D-glucopyranosyl-3-hydroxynodakenetin (14) and phenylethyl-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (15).
CONCLUSIONAll of these compounds were isolated from this plant for the first time and most of them are furocoumarins.
Benzopyrans ; chemistry ; Bignoniaceae ; chemistry ; Caffeic Acids ; chemistry ; Coumarins ; chemistry ; Furans ; chemistry ; Furocoumarins ; chemistry ; Magnetic Resonance Spectroscopy ; Methoxsalen ; analogs & derivatives ; chemistry ; Molecular Structure
2.Influence of different processing motivation on the intergroup interaction willingness of college students
Yatong LI ; Haoyang BAI ; Xiaolong FU ; Xiaobin DING
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(4):334-340
Objective:To explore the effect and mechanism of different processing motivation on college students' intergroup interaction willingness by technology of eye movement.Methods:Sixty college students conforming to the study conditions were selected from Northwest Normal University and randomly divided into ingroup motivation group ( n=30) and outgroup motivation group ( n=30) according to the random number table method. Subjects of the two groups first participated in the eye movement task, and then participated in the partner selection task.In the eye movement task, the percentage of time that subjects looked at faces of different groups was recorded.And in the partner selection task, the number of selections that subjects selected faces from different groups was recorded.SPSS 20.0 software was used for repeated measurement analysis of variance. Results:(1) In the eye movement task, there was a significant interaction of group and face group type ( F=13.37, P<0.001), but the main effects of group( F=3.23, P=0.077), and face group type ( F=0.09, P>0.05) were not significant. Further simple effect analysis showed that the percentage of time that the ingroup motors looked at the yellow race((16.00±0.06)%) was significantly higher than that of the outgroup motors ((12.00±0.04)%), and the percentage of time that the outgroup motors looked at the white race((17.00±0.06)%) was significantly higher than that of the ingroup motors ((9.00±0.04)%). (2) In the task of partner selection, there was a significant interaction among group, face group type and face old and new types( F=4.38, P=0.041), and the main effect of face group type was significant( F=14.87, P<0.001). The main effect of old and new types of face was significant( F=8.88, P=0.004), but the main effect of group was not significant ( P>0.05). Further simple effect analysis showed that the two groups of college students had statistically significant differences in the selection times of familiar faces from different groups( F=11.51, P=0.001). The number of times that the ingroup generator (5.51±1.14) selected the familiar yellow race as its partner was significantly greater than that of the outgroup generator (2.30±0.65). The number of times that the outgroup generator (5.40±1.00) selected the familiar white race as its partner was significantly greater than that of the ingroup generator (3.47±0.94). (3)Preferential attention to the ingroup members was a mediator between processing motivation and intergroup interaction willingness (mediating effect=0.20, 95% CI=0.02-0.31). Conclusion:Ingroup processing motivation has a threatening effect on college students' intergroup interaction willingness, outgroup processing motivation has a promoting effect on college students' intergroup interaction willingness, and processing motivation affects intergroup interaction willingness through ingroup bias.
3.Quantitative analysis of gene expression for vascular endothelial growth factor and its application.
Xia BAI ; Jian-Xin FU ; Kai-Yang DING ; Jian-Nong CEN ; Wei WANG ; Chang-Geng RUAN
Journal of Experimental Hematology 2005;13(4):548-552
Vascular endothelial growth factor (VEGF), a central mediator of angiogenesis, not only plays an important role in the pathogenesis of leukemia, but also is an independent prognostic factor in patients with hematologic malignancies, like those in solid tumors. However, the importance of VEGF during differentiation or apoptosis of leukemia cells remains to be elucidated. In order to assess the alternation of VEGF gene expression in the process of all-trans retinoic acid (ATRA)-induced differentiation of NB4 acute promyelocytic leukemia cell line, and a competitor DNA fragment, VEGF gene competative template (T-VEGFDelta) was constructed by using gene recombinant technologies, and a competitive quantitative reverse transcriptase-polymerase chain reaction (cQRT-PCR) method was developed. A standard curve was obtained by co-amplification of serial dilutions of the target nulecules with constant amount of competitive template and this curve was used to detect molecular number of target gene in measuring sample. The surface expression of CD11b antigen and nitroblue tetrazolium (NBT) reduction rate of NB4 cells were also assayed at different time points. The results showed that cQRT-PCR was a sensitive, reliable tool for analysis of VEGF gene expression with a detectable range from 1 x 10(4) to 2 x 10(5) molecules. The number of VEGF gene transcripts detected by means of cQRT-PCR assay was 42.3 x 10(5), 12.6 x 10(5), 3.6 x 10(5), and less than 1.0 x 10(5)/microg total RNA at 0, 12, 24 and 48 hours after ATRA treatment, respectively. This rapid down-regulation of VEGF gene expression, during ATRA-induced NB4 cell differentiation, was accompanied by the up-regulation of CD11b expression and an increased NBT reduction rate. In conclusion, cQRT-PCR method was successtully constructed, confirming that ATRA efficiently repressed VEGF, at the same time, the ATRA might exert an antileukemic effect, other than induction of differentiation via inhibition of angiogenesis.
Antineoplastic Agents
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pharmacology
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CD11b Antigen
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genetics
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Cell Differentiation
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drug effects
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genetics
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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drug effects
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Humans
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Leukemia, Promyelocytic, Acute
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genetics
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pathology
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Molecular Sequence Data
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Reverse Transcriptase Polymerase Chain Reaction
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methods
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Tretinoin
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pharmacology
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Vascular Endothelial Growth Factor A
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genetics
4.Effects of ICAM-1 gene K469E, K56M polymorphisms on plasma sICAM-1 expression levels in Chinese Yugur, Tibetan and Han nationalities.
Ming-Ying WANG ; De-Cheng BAI ; Ping ZHU ; Yu FU ; Ding-Fang BU ; Ying ZHANG
Journal of Experimental Hematology 2012;20(5):1205-1211
This study was purposed to investigate the intercellular cell adhesion molecule-1 (ICAM-1) gene K469E (A/G) (rs5498) and K56M (A/T) (rs5491) single nucleotide polymorphisms (SNP) and soluble ICAM-1 (sICAM-1) levels in plasma in three Chinese populations of Yugur, Tibetan and Han nationalities, to analyze comparatively the genotypes and allele frequencies distribution in different ethnic groups, and to explore the effects of ICAM-1 K469E and K56M polymorphism and sICAM-1 levels in plasma. EDTA-anticoagulant venous blood from Yugur(327 cases), Tibetan (400 cases) and Han (126 cases) people was collected, the DNA was extracted by using whole blood genomic DNA extraction kit, DNA SNP were analyzed by PCR-RFLP, genotype was judged by gel scan imaging system after agarose gel electrophoresis, the gene sequence was determined and the distribution of ICAM-1 genotypes and allele frequencies were compared among different ethnic groups, besides, the group representativeness was tested via the Hardy-Weinberg genetic equilibrium. Finally, the human sICAM-1 plasma levels were detected by using human ICAM-1 ELISA kit. The results showed that DNA sequencing result was consistent with PCR-RFLP analysis. In Yugur, Tibetan and Han nationalities, the KK, KE and EE three genotypes at ICAM-1 K469E gene locus were detected, the genotype distribution was not statistically significantly different, while the K, E allele frequency distribution was statistically significantly different (P < 0.05). Both of genotype and allele frequency distribution between Yugur, Tibetan and Han nationalities were statistically significantly different (P < 0.05). In K56M site only KK, KM two genotypes were detected, but the MM genotype was not detected in the three ethnic groups; the difference of two genotypes and K, M allele frequencies between Yugur and Han population was statistically significantly different (P < 0.05). Among three ethnic groups, the sex ratio and age distribution of K469E, K56M genotypes and allele frequencies of ICAM-1 gene were not significantly different, and distribution was in accordance with Hardy-Weinberg genetic equilibrium (P > 0.05). The plasma sICAM-1 level at ICAM-1 K469E allele locus in K individuals [(253 ± 122), (185 ± 97) µg/L] was higher than that at non-K allele [(145 ± 110) µg/L, P < 0.01]; the plasma sICAM-1 level of ICAM-1 K56M sites with KK genotype [(253 ± 122) µg/L] was higher than that of the KM genotypes [(168 ± 103) µg/L, P < 0.01]. In Yugur and Tibetan groups, the plasma sICAM-1 levels [(224 ± 80), (214 ± 111) µg/L] were higher than that in the Han group [(175 ± 125)µg/L, P < 0.05]. Pairwise comparison indicated that the plasma sICAM-1 levels between Yugur and Han group were statistically significantly different (P < 0.01), that was significantly different between Tibetan and Han group (P < 0.05). It is concluded that in Yugur, Tibetan and Han population, the genotypes and gene frequencies of two amino acid sites K469E and K56M in ICAM-1 were KK/KE-type, KK-type and K allele, moreover, the ratio of them in Yugur and Tibetan group was higher than that in Han, while there is not significant difference in sex ratio and age distribution, therefore, ICAM-1 genotype and allele frequency distribution in this study had ethnic representativeness. ICAM-1 gene K469E and K56M polymorphisms were likely to affect the plasma sICAM-1 expression level. K469E gene K allele may be a genetic risk factor, while K56M gene M allele a may be genetic protective factor for some diseases.
Adolescent
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Adult
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Aged
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Asian Continental Ancestry Group
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genetics
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Ethnic Groups
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genetics
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Female
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Gene Frequency
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Genotype
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Humans
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Intercellular Adhesion Molecule-1
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blood
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genetics
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Male
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Middle Aged
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Plasma
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metabolism
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Polymorphism, Genetic
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Young Adult
5.A1381T and -1793G/C polymorphisms of vWF gene impact the plasma vWF levels in Yugur, Tibetan and Han nationalities of China.
Yu FU ; Ping ZHU ; Ding-Fang BU ; Ying ZHANG ; Ming-Ying WANG ; Yi-Wen GONG ; De-Cheng BAI
Journal of Experimental Hematology 2012;20(5):1200-1204
The aim of this study was to investigate the similarities and differences of A1381T (rs216311) and -1793G/C (rs7966230) single nucleotide polymorphisms (SNP) in Chinese Yugur, Tibetan, and Han nationalities and their influence on plasma vWF concentration in order to explore the sensitivity of these 3 nationalities to vWF-related diseases. Peripheral venous blood was obtained from 322 Yugur, 399 Tibetan, and 120 Han healthy people. The DNA were then extracted. vWF gene A1381T and -1793G/C polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequenced when it was necessary. The vWF:Ag level in plasma was determined by ELISA. The results showed that the genotype distribution of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han nationalities was different with statistically significance (P < 0.05). GG genotype of A1381T locus accounted for 69.9% in Yugur nationality, which was much higher than 56.6% and 53.3% in Tibetan and Han nationalities respectively(P < 0.01); AA genotype of A1381T locus expressed a low level of vWF in plasma. For the -1793G/C locus, the proportion of CG genotype in Yugur was much higher than that in Han, CC genotype expressed a high level of vWF in plasma. The plasma vWF levels with different nationalities and the polymorphism of vWF gene were significantly different. It is concluded that the polymorphisms of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han are significantly different; the polymorphism of vWF gene influences the plasma vWF level; the plasma vWF levels in Yugur and Tibetan are significantly higher than that in Han, which may be associated with the living environment and habits.
Adolescent
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Adult
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Aged
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Asian Continental Ancestry Group
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genetics
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China
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Ethnic Groups
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genetics
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Female
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Gene Frequency
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Genotype
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Humans
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Male
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Middle Aged
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Plasma
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chemistry
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Polymorphism, Genetic
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Young Adult
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von Willebrand Factor
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genetics
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metabolism
6.Clinical value of radiomics based on CT examination in preoperative differential diagnosis of pancreatic serous cystadenoma and mucinous cystadenoma
Wenjie LIANG ; Wuwei TIAN ; Yubizhuo WANG ; Jingwen XIA ; Shijian RUAN ; Jiayuan SHAO ; Zhihao FU ; Na LU ; Yong DING ; Wenbo XIAO ; Xueli BAI
Chinese Journal of Digestive Surgery 2021;20(5):555-563
Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.
7.Hepatic epithelioid hemangioendothelioma: a case report.
Fu-rong SUN ; Web-heng ZHENG ; Bing-yuan WANG ; Hai WANG ; Ran AO ; Fei WANG ; Ping-ping ZHENG ; Yuan-yuan DING ; Bai-fang WANG
Chinese Journal of Hepatology 2012;20(12):951-952
8.Polymorphisms of estrogen-metabolizing genes and breast cancer risk: a multigenic study.
Ding-Fen HAN ; Xin ZHOU ; Ming-Bai HU ; Wei XIE ; Zong-fu MAO ; Dong-e CHEN ; Fang LIU ; Fang ZHENG
Chinese Medical Journal 2005;118(18):1507-1516
BACKGROUNDEndogenous estrogen plays a very important role in the carcinogenesis and progression of breast cancer. The enzymes involved in the biosynthesis and metabolism of estrogen have been proposed to contribute to this effect. To examine this hypothesis, we conducted a case-control study to investigate the relationship between polymorphisms of genes responsible for estrogen biosynthesis (CYP17, cytochrome P450c17a and CYP19, aromatase cytochrome P450) and estrogen sulfation of inactivation (SULT1A1, sulfotransferase1A1) and the risk of breast cancer in Chinese women.
METHODSThis study involved 213 breast cancer patients and 430 matched controls. PCR-based restriction fragment length polymorphism (RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the mononucleotide transition of CYP17 and SULT1A1 and tandem repeat polymorphism of CYP19. Logistic regression analyses were used to determine OR and 95% CI of each and all three high-risk genotypes, of all three genotypes combined, and of estrogen exposure factors. The relationship between each high-risk genotype and clinicalpathological characteristics were also assessed.
RESULTSThe frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P = 0.82). The frequency of His allele of SULT1A1 was significantly higher in cases (13.6%) than in controls (9.5%) (P < 0.05). There was also significant difference of the (TTTA) 10 allele of CYP19 which was 12.4% in cases and 8.2% in controls (P < 0.05). When the CYP17 A2 allele, CYP19 (TTTA) 10 and SULT1A1 His allele were considered as the "putative high-risk" genotype, there was an increased risk of breast cancer with the number of high-risk genotypes in a dose-response effect (trend, P = 0.05). In multivariate analysis, the SULT1A1 genotype remained the most significant determinant for breast cancer, with OR = 2.37 (95% CI 1.23-4.74), followed by CYP19, with OR = 1.75 (95% CI 1.27-3.56). The (TTTA) 10 allele of CYP19 was associated with tumor size, and the His allele of SULT1A1 associated with status of lymph node metastasis.
CONCLUSIONSThis study supports the hypothesis that breast cancer can be initiated by estrogen exposure and that estrogen metabolizing genes are involved in this mechanism. This multigenic model is useful for identifying individuals who are at higher risks of breast cancer.
Adult ; Aged ; Aromatase ; genetics ; Arylsulfotransferase ; genetics ; Breast Neoplasms ; etiology ; genetics ; Case-Control Studies ; Estrogens ; metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Steroid 17-alpha-Hydroxylase ; genetics
9.Different treatment modalities of fusiform basilar trunk aneurysm: study on computational hemodynamics.
Chen WU ; Bai-Nan XU ; Zheng-Hui SUN ; Fu-Yu WANG ; Lei LIU ; Xiao-Jun ZHANG ; Ding-Biao ZHOU
Chinese Medical Journal 2012;125(1):97-101
BACKGROUNDUnclippable fusiform basilar trunk aneurysm is a formidable condition for surgical treatment. The aim of this study was to establish a computational model and to investigate the hemodynamic characteristics in a fusiform basilar trunk aneurysm.
METHODSThe three-dimensional digital model of a fusiform basilar trunk aneurysm was constructed using MIMICS, ANSYS and CFX software. Different hemodynamic modalities and border conditions were assigned to the model. Thirty points were selected randomly on the wall and within the aneurysm. Wall total pressure (WTP), wall shear stress (WSS), and blood flow velocity of each point were calculated and hemodynamic status was compared between different modalities.
RESULTSThe quantitative average values of the 30 points on the wall and within the aneurysm were obtained by computational calculation point by point. The velocity and WSS in modalities A and B were different from those of the remaining 5 modalities; and the WTP in modalities A, E and F were higher than those of the remaining 4 modalities.
CONCLUSIONSThe digital model of a fusiform basilar artery aneurysm is feasible and reliable. This model could provide some important information to clinical treatment options.
Adult ; Computational Biology ; Hemodynamics ; physiology ; Humans ; Intracranial Aneurysm ; diagnostic imaging ; pathology ; physiopathology ; Male ; Radiography
10.Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats.
Xue-Mei OU ; Bai-Ding WANG ; Fu-Qiang WEN ; Yu-Lin FENG ; Xiang-Yang HUANG ; Jun XIAO
Chinese Medical Journal 2008;121(17):1680-1687
BACKGROUNDMucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).
METHODSMucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR), immunohistochemistry or Western blotting. Tumor necrosis factor (TNF)-alpha and IL-8 in bronchoalveolar lavage fluid (BALF) were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).
RESULTSSimvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P <0.05). Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-alpha and IL-8 in BALF follows LPS stimulation (P < 0.05). The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P <0.05). Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P < 0.05). However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration.
CONCLUSIONSSimvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and inflammatory cytokine release via inactivation of RhoA and p38 signaling pathway.
Animals ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Lipopolysaccharides ; toxicity ; Male ; Mucin 5AC ; secretion ; Rats ; Rats, Sprague-Dawley ; Respiratory Mucosa ; drug effects ; secretion ; Simvastatin ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; rhoA GTP-Binding Protein ; antagonists & inhibitors