1.Comparison of PG-SGA, NRS 2002 and BIA in nutritional assessment and screening of patients with gynecologic cancers
Yongning CHEN ; Yang GUAN ; Li ZHENG ; Wenlian LIU ; Chunhua WU ; Yadi ZHANG ; Li CHEN ; Shipeng GONG
Parenteral & Enteral Nutrition 2017;24(4):221-224
Objective:To evaluate the application of PG-SGA,NRS 2002 and BIA in nutritional assessment and screening of patients with gynecologic cancers.Methods:118 patients were randomly selected.Nutritional status were evaluated by PG-SGA,NRS 2002 and BIA,and consistency between each tools were compared.Results:The prevalence of malnutrition or nutritional risk of patients were 64.4% (PG-SGA),57.6% (NRS 2002),and 33.9% (BIA) respectively.In all patients,the consistency of PG-SGA and NRS 2002 was high (P < 0.001),while there were not significantly consistent between BIA and PG-SGA,or between BIA and NRS 2002 (P < 0.001).Conclusion:According to the evaluation of PG-SGA or NRS 2002 in gynecologic patients,the prevalence of malnutrition or nutritional risk is high,and these two scales are suitable for nutritional assessment and screening of gynecologic cancer patients,especially in ovarian cancer patients.In addition,BIA may be a promising tool to evaluate cervical cancer patients' nutritional status.
2.The expression of PD-L2 in human cervical carcinomas and the influence to peripheral blood T lymphocytes apoptosis
Weipu GENG ; Man XU ; Yan ZHANG ; Yu CHEN ; Wenlian HUANG ; Tingting WANG
Chongqing Medicine 2014;(9):1052-1054,1057
Objective To determine PD-L2 expression in human cervical squamous cell carcinomas and analyze its association with the clinical and pathologic characteristics of these cases ;observe the role of recombinant PD-L2 protein on apoptosis of active peripheral blood T lymphocytes of cervical carcinoma patients .Methods PD-L2 expression in cervical squamous cell carcinomas was determined by immunohistochemistry staining ,and the association between PD-L2 expression with the clinical and pathologic characteristics of these cases was analyzed .In vitro ,the peripheral blood T lymphocytes of cervical carcinoma patients were divided into blank group ,PD-L2 group and PD-L2+anti-PD-1 group respectively .After these active T cells were cultured 72 h ,their apop-totic rates were detected by flow cytometry .Results PD-L2 expressed in 53 .3% (32/60)cervical squamous cell carcinomas ,and it′s expression associated with lymph node metastasis of these cases (P< 0 .05) .In vitro ,PD-L2 promoted apoptosis of CD4+ T and CD8+ T lymphocytes ,the apoptotic rates were 17 .0% and 22 .4% respectively ,which were higher than 9 .0% and 16 .2% of blank group;however ,the apoptotic rates dropped to 11 .1% and 17 .5% in PD-L2+anti-PD-1 group .Conclusion PD-L2 aberrantly ex-presses in cervical squamous cell carcinomas and is associated with their lymph node metastasis .PD-L2 promotes apoptosis of T lymphocytes and depresses the anti-tumor immunity of cervical microenvironment ,and promotes lymph node metastasis of these cancers .PD-L2/PD-1 pathway may be a potential immunotherapy target of cervical squamous cell carcinomas .
3.Influence of B7-H4 on cell proliferation,apoptosis and cytokine secretion of peripheral blood activated T cells in cervical cancer patients
Yan ZHANG ; Tingting WANG ; Man XU ; Wenlian HUANG ; Wei LUO ; Lin XIAO
Chongqing Medicine 2015;(26):3628-3630,3633
Objective To observe the in vitro influence of recombinant human B7-H4 protein on the cell proliferation cycle, apoptosis and cytokine secretion of peripheral blood activated T lymphocytes in cervical cancer patients.Methods After 48 h co-culture of peripheral blood T lymphocytes in 1 5 cases of cervical cancer with B7-H4 48 h,T lymphocytes′cell proliferation cycle, apoptosis and T lymphocytes subtypes changes were detected by FCM;the cytokines concentration in the culture supernatant was tested by ELISA array.Results After 48 h co-culture of peripheral blood T lymphocytes with B7-H4 48hs,G1,G2 and S phase of T cells accounted for 90.59%,8.55% and 0.87% respectively,which of the blank group were 92.83%,6.09% and 1.13% respec-tively;the Ki67 positive rates of CD4 + T and CD8 + T cells in the B7-H4 group were 2.13%±0.13% and 1.03%±1.33% respec-tively,which of the blank group were 2.74% ±0.98% and 1.71% ± 1.32% respectively;the proportion of CD4 + T and CD8 + T cells accounting for T cells in the B7-H4 group was decreased compared with the blank group,but the ratio of CD4 + T/CD8 + T and the proportion of CD4 + CD25 + Foxp3 + T cells were increased,in addition,the TGF-β1 secretion;concentration in the co-culture su-pernatant in the B7-H4 group was (259.25±32.78)pg/mL,which was higher than (202.75 ±20.1 7)pg/mL in the blank group. B7-H4 had no significant influence on the peripheral blood activated T cells apoptosis.Conclusion B7-H4 block the peripheral blood activated T cells at G2 phase,the S phase cells are obviously decreased;B7-H4 inhibits the cellular proliferation of CD4 + T and CD8 + cells,but may have the promoting effect on Foxp3 + T proliferation and TGF-β1 secretion;B7-H4 has no significant influ-ence on T cell apoptosis.B7-H4 plays a role in depressing anti-tumor T cell immune response of cervical cancer and may become a potential target of cervical cancer immunotherapy.
4.Relationship between fibular head height and varus knee osteoarthritis occurrence and severity
Wenru MA ; Lei DING ; Shengnan SUN ; Zengshuai HAN ; Wenlian SONG ; Yi ZHANG ; Jinli CHEN ; Haitao FU ; Yingze ZHANG ; Tengbo YU
Chinese Journal of Orthopaedics 2021;41(14):985-991
Objective:To explore the correlation between fibular head height and varus knee osteoarthritis occurrence and severity.Methods:A retrospective analysis was performed on 618 participants (618 knees, 184 males and 434 females, mean age 61.12±10.98 years) who underwent standard weight-bearing full-leg radiographs and were diagnosed as non-knee osteoarthritis or varus knee osteoarthritis from January 2019 to June 2019. Knee osteoarthritis was diagnosed according to Kellgren-Lawrence grading: 0-I grades were diagnosed as non-osteoarthritis, II-IV grades were diagnosed as osteoarthritis. Joint line convergence angle (JLCA), medial proximal tibial angle (MPTA) and hip-knee-ankle angle were measured on X-rays to reflect varus deformity. The fibular head height was defined as the vertical distance from upper edge of fibular head to lateral tibial plateau. Patients were divided into 5 groups according to Kellgren-Lawrence grading. Differences of age, gender, height, weight, body mass index, varus deformity (JLCA, MPTA and hip-knee-ankle angle) between Kellgren-Lawrence 0-IV grades were compared. Ordinal logistic regression was performed to analyze the correlation between fibular head height and Kellgren-Lawrence grades. Pearson's correlation analysis was used for the correlation among fibular head height, JLCA, MPTA and hip-knee-ankle angle, and the main factor of JLCA, MPTA and hip-knee-ankle angle was extracted by factor analysis. Multiple linear regressions were used to analyze the correlation between fibular head height and varus deformity score.Results:There were 68, 66, 97, 98, 289 participants in Kellgren-Lawrence grades 0-IV respectively that was 134 participants were diagnosed as non-osteoarthritis and 484 participants were diagnosed as osteoarthritis. Fibular head height and MPTA showed a decreasing trend ( F=129.076, 24.875; P<0.001) while JLCA and hip-knee-ankle angle showed an increasing trend ( F=414.346, 105.996; P<0.001) with the increase in Kellgren-Lawrence grading. Age, body mass index and fibular head height are influencing factors of Kellgren-Lawrence grading with OR(95%CI) were 1.116(1.093, 1.141), 1.363(1.060, 1.754), 0.617(0.575, 0.662) . Fibular head height was negatively correlated with JLCA and hip-knee-ankle angle ( r=-0.641, -0.478; P<0.001) , respectively, and positively correlated with MPTA ( r=0.320, P<0.001). There were significant correlations between age, fibular head height and the varus deformity score ( β=0.274, -0.457; P<0.001). Conclusion:Fibular head height of patients with varus knee osteoarthritis is lower than that of non-osteoarthritis. In addition to age and body mass index, fibular head height is a risk factor for varus knee osteoarthritis occurrence. The smaller the fibular head height is, the more serious the osteoarthritis severity and varus deformity are.
5.Extraperitoneal transumbilical single-port laparoscopic radical prostatectomy: A report of 11 cases
Tianxin LIN ; Jian HUANG ; Chun JIANG ; Kewei XU ; Feng YE ; Hai HUANG ; Jinli HAN ; Yousheng YAO ; Wenlian XIE ; Caixia ZHANG ; Wen DONG ; Hao LIU
Chinese Journal of Urology 2011;32(2):94-98
Objective To present our initial experience in laparoscopic radical prostatectomy performed through an umbilical incision using a home-made multichannel port. Methods From August 2009 to March 2010, we performed single-port laparoscopic radical prostatectomy in 11 patients with localized prostate cancer. A home-made multichannel port was inserted extraperitoneally through a 3-cm umbilical incision. The single port extraperitoneal procedures included obturator fossa lymphadenectomy, radical prostatectomy and urethro-vesical anastomosis, while the urethro-vesical anastomosis was performed by a slip-knot running suture technique. Data were collected and analyzed prospectively. Results All cases were completed successfully, without conversion to a standard laparoscopic approach or open surgery except adding an additional port in one case. The average operative time was 256 minutes (range195-315), and the mean blood loss was 90 ml (range 20- 180), without any blood transfusion. The postoperative hospital stay was 15.4 days (range13- 24), and the Foley catheter was removed 12 days after surgery. No intraoperative complications occurred. One patient developed a vesico-rethralanastomosis leakage, 2 had lymphatic leakage and 1 had urinary tract infection,all of the cases were managed successfully with conservative treatment. Histopathological results showed negative surgical margine and negative lymph node dissection. All patients had no biochemical relapse after an average follow-up of 7 months. Conclusions Single-port laparoscopic radical prosta tectomy is feasible, cosmetic and minimally invasive with a low complication rate and good short-term outcome. Additional investigation is needed to evaluate the long-term safety and oncologic adequacy of this new approach.
6.Effect and mechanism of mesenchymal stem cell derived exosomes in repair of tendon cell injury
Haibo ZHAO ; Xia ZHAO ; Jiake GAO ; Wenlian SONG ; Zhengyi SHAN ; Tengbo YU ; Yingze ZHANG
Chinese Journal of Trauma 2021;37(7):653-661
Objective:To investigate the effects and mechanism of exosomes secreted by human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in repair of tendon cell injury.Methods:The hUC-MSCs which were stably subcultured were isolated and purified by a tissue block adherent method,and the immunophenotype of hUC-MSCs was detected by flow cytometry. The induction media was employed to induce the differentiation of hUC-MSCs to osteoblasts,chondroblasts and adipocytes,and cell identification was performed subsequently. The secreted exosomes of MSCs (MSCs-exosomes) were extracted using an ultracentrifugation method. The exosomes were detected by Western blot and electron microscopy,and the fusion ability of the exosome membrane was detected by PKH67 staining fluorescence. Forty Wistar rats were divided into tendon injury group ( n = 20) and normal group ( n = 20) according to the random number table. In tendon injury group,the rats were sacrificed with 100 mg/kg pentobarbital sodium one week after Achilles tendon transection,and the injured tendon cells were obtained following digestion of the Achilles tendon. In normal group,the rats were sacrificed without any treatment and the normal tendon cells were obtained concurrently. After the exosomes were co-cultured with tendon cells in vitro for 12,24,48,72 hours,the proliferation of tendon cells was detected by CCK-8 assay. After the tendon cells were treated with hUC-MSCs exosomes for 24 hours,the effects of exosomes on transforming growth factor β (TGF-β),bone morphogenetic protein (BMP),vascular endothelial growth factor (VEGF),fibroblast growth factor (FGF),interleukin(IL)-1β and tumor necrosis factor-α (TNF-α) were detected by Western blot,qPCR and immunofluorescence. Results:The hUC-MSCs were identified and hUC-MSCs-exosomes were isolated successfully. The cultured MSCs were fusiform and positive for Alanine aminopeptidase (CD13),integrin β-1 (CD29),ECTO-5'-nucleotidase (CD73),thymocyte surface antigen (CD90) and endothelin (CD105),but negative for human leukocyte DR antigen (HLA-DR),hematopoietic progenitor cell antigen (CD34) and leukocyte common antigen (CD45). The exosomes isolated showed a round disc shape and a diameter of 30-100 nm with a depressed internal structure under the electron microscope which was verified via PKH67 staining and the motility-related protein-1 (CD9) and lysosomal associated membrane protein 3 (CD63) were highly expressed. The CCK-8 assay showed the cell viability in tendon injury group was markedly higher than that in normal group at 12 h,24 h,48 h,and 72 h following treatment of tendon cells ( P < 0.01). The results of qPCR revealed that the mRNA expressions of TGF-β (1.850 ± 0.127),BMP (2.133 ± 0.398),FGF (1.610 ± 0.223) and VEGF (2.207 ± 0.059) in tendon injury group were markedly higher than those in normal group(1.004 ± 0.105,1.007 ± 0.145,1.007 ± 0.140,1.001 ± 0.065,respectively) ( P < 0.05). However,the mRNA expressions of IL-1β (0.102 ± 0.009) and TNF-α (0.130 ± 0.013) in tendon injury group was markedly lower than those in normal group (1.004 ± 0.113,1.006 ± 0.134) ( P < 0.01). The results of Western blot were consistent with those of qPCR. Conclusions:The exosomes secreted by hUC-MSCs can promote the growth of tendon cells and repair of tendon cell injury by up-regulating the expression of growth factors TGF-β,BMP,VEGF and FGF,and inhibiting the expression of inflammatory factors IL-1β and TNF-α.
7.Modified versus traditional open wedge high tibial osteotomy for varus knee osteoarthritis
Chunpu LI ; Jiayi FAN ; Yi ZHANG ; Wenlian SONG ; Shenjie SUN ; Chao QI ; Tengbo YU ; Jinli CHEN
Chinese Journal of Orthopaedic Trauma 2023;25(11):944-951
Objective:To compare the clinical efficacy between modified open wedge high tibial osteotomy (MOWHTO) versus traditional open wedge high tibial osteotomy (TOWHTO) for varus knee osteoarthritis (KOA).Methods:A retrospective study was conducted to analyze the 50 patients (60 knees) with varus KOA who had received high tibial osteotomy at Department of Sports Medicine, The Affiliated Hospital of Qingdao University between September 2019 and December 2020. The patients were divided into 2 groups according to different ways of osteotomy: a traditional group and a modified group. In the traditional group subjected to TOWHTO, there were 25 cases (30 knees); in the modified group subjected to MOWHTO, there were 25 cases (30 knees). In MOWHTO, the bone block attached to the medial collateral ligament (MCL) of the knee was first chiseled at the MCL insertion before osteotomy to reduce excessive stripping of the MCL in the osteotomy area, and then the bone fragment attached to the MCL was filled into the osteotomy area to increase bone filling and bone coverage after the alignment of the lower limb was corrected. The hip-knee-ankle angle (HKAA), medioproximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured preoperatively and at 18 months postoperatively in both groups to evaluate correction of the alignment of the lower limb. Fracture healing time, bone loss in the osteotomy area, Hospital for Special Surgery (HSS) knee score and visual analogue scale (VAS) were recorded to evaluate the postoperative efficacy.Results:There was no statistically significant difference between the TOWHTO and MOWHTO groups in the general clinical data before operation, showing comparability ( P>0.05). At 18 months after operation, HKAA was (179.1° ± 1.1°) in the TOWHTO group and (179.3° ± 0.7°) in the MOWHTO group while MPTA was (91.9° ± 0.4°) in the TOWHTO group and (91.9° ± 0.4°) in the MOWHTO group, showing no statistically significant difference between the 2 groups ( P>0.05) but a significant difference between preoperation and postoperation in each group ( P<0.05). At 18 months after operation, JLCA was (1.8° ± 0.4°) in the TOWHTO group, significantly larger than that in the MOWHTO group (1.5° ± 0.4°), HSS score was 81.5 (79.5, 83.0) points in the TOWHTO group, significantly lower than that in the MOWHTO group [85.0 (82.5, 87.5) points], and VAS was 1.8 (1.6, 2.0) points in the TOWHTO group, significantly higher than that in the MOWHTO group [1.5 (1.5, 2.0) points] (all P<0.05). At 18 months after operation, the preoperative JLCA was significantly improved in both groups ( P<0.05). The time required for a fracture healing score higher than 4 points was (3.3 ± 0.6) months in the TOWHTO group and (4.5 ± 0.9) months in the MOWHTO group, and the rate of bone loss in the osteotomy area was 20% in the TOWHTO group (6/30) and 0 (0/30) in the MOWHTO group, both showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both TOWHTO and MOWHTO can effectively treat varus KOA. MOWHTO is more effective in promoting bone healing in the osteotomy area, reducing bone defects in the osteotomy area and improving knee function.
8.Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis
Wentao CHEN ; Xiaoxiang WANG ; Wenlian ZHENG ; Weiqiang ZHANG ; Lujia MAO ; Jianan ZHUO ; Sitong ZHOU ; Ronghua YANG
Chinese Journal of Burns 2024;40(4):333-341
Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.
9.Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis
Duohao WANG ; Wenlian YIN ; Xiuyi PAN ; Mengni ZHANG ; Ling NIE ; Xueqin CHEN ; Hao ZENG ; Qiao ZHOU ; Ni CHEN
Chinese Journal of Pathology 2024;53(8):789-796
Objective:To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined.Methods:Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted.Results:The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.216). Conclusions:The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.
10.Intervention effect and mechanism of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis mice
Xinxin WANG ; Xiaoyan CHEN ; Sijia LI ; Wenlian ZHANG ; Kun WANG ; Deqiang DOU
China Pharmacy 2023;34(17):2079-2084
OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis (AD) mice,and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups,i.e. normal control group (group A),model group (group B),dexamethasone intervention group (positive control,group C),H. rhamnoides oil intervention group (group D),dexamethasone+H. rhamnoides oil intervention group (group E),with 10 mice in each group. Except for group A,other groups were given 2,4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment,groups C,D and E were given dexamethasone (1.5 mg/kg) and/or H. rhamnoides oil (10 mL/kg) intragastrically,once a day,for 28 consecutive days. After the last medication,the pathomorphological changes of ear tissue were observed by 节作用。E-mail:57667478@qq.com HE staining; the serum levels of immunoglobulin E (IgE) and interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α (GRα) and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein,GRβ protein,and protein kinase B (AKT)/ribosomal protein S6 kinase 1,S6K1 (S6K1) signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B,the skin inflammation in the left ear of the mice was significantly reduced in groups C,D and E,the serum levels of IgE and IL-4 were decreased significantly in groups D and E (P< 0.05),while the number of GRα positive cells and GRα protein expression were increased significantly (P<0.05); the protein levels of G protein inhibitory subunit 1 (Gαi1),Gαi3,phosphorylated S6K1 (p-S6K1) and phosphorylated AKT (p-AKT) were decreased significantly (P<0.05); the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E(P<0.05). Compared with group C,the skin inflammation in the left ear of the mice was almost clear away in group E,the serum levels of IgE and IL-4 were decreased significantly (P<0.05); the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E (P<0.05); the protein levels of GRβ,Gαi1,p-S6K1 and p-AKT were all decreased significantly in groups D and E(P<0.05); and protein level of Gαi3 was decreased significantly in group E (P<0.05). CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice,which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.