1.Investigation on the Relationship of H2S and the Accumulation of Extracellular Matrix of the Diabetic Nephropathic Rats By BrdU labeling method
Shen CHEN ; Wen HUANG ; Mei ZHANG ; Guojuan ZHANG
Journal of Medical Research 2017;46(5):112-115
Objective To explore the relationship of hydrogen sulfide (H2S) and the extracellular matrix of the diabetic nephropathic rats' glomerulars.Methods Twenty-one male rats(Sprague-Dawley) were randomly divided into Control group(n =7),DN group (n =7) and DN + H2 S group (n =7).Diabetes was induced in the rats except Control group rats by STZ (60mg/kg).The rats of the DN + H2S group were injected with NaHS every day,and rats of other groups were injected with NS.Eight weeks later,three groups were compared in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars.Results Compared with Control group,DN group rats were significantly increased in proteinuria of 24 hours and KW/BW (P < 0.01).Kidney biopsy in DN groups rats were typical DN pathological manifestation.In treatment with NaHS,the DN rats in the DN + H2S group were decreased in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars (P < 0.01),and was similar with the control group in the pathology of renal.Conclusion The H2 S control the multiplication of myofibroblast,and were decreased in the distribution of α-SMA in glomerulars.The H2S treatment may put off the progress of the extracellular matrix in the DN rats' glomerulars.
2.Ulinastatin attenuates lipopolysaccharide-induced acute lung injury by intervening p38 MAPK/ERK signaling pathway
Lipeng ZHANG ; Yan ZHAO ; Guojuan LIU ; Dagang YANG ; Lihua ZHOU
Chinese Pharmacological Bulletin 2016;32(9):1311-1316
Aim To investigate whether ulinastatin has a beneficial effect on lipopolysaccharide( LPS) induced acute respiratory distress syndrome ( ARDS ) in rats, and to explore the possible underlying mechanisms. Methods Fifty-six Wistar rats were randomly as-signed into control group, model group( LPS 6,12,24 h groups), ulinastatin group(UTI 6,12,24 h groups), with 8 in each group. ARDS rat model was reproduced by intraperitoneal injection of LPS ( 10 mg · kg-1 ) , The rats in UTI groups were injected ulinastatin (20 000 u·kg-1), The rats in the control group re-ceived an equal volume of normal saline at the same time, rats in each group were sacrificed at 6,12,24 hours after LPS challenge. Plasma and lung tissue sam-ples were collected, Histopathological evaluation, lung wet/dry (W/D) ratio, Tumor necrosis factor-a(TNF-α) , Interleukin-18 ( IL-18 ) , surfactant protein A ( SPA) , malondialdehyde ( MDA ) , nitric oxide ( NO ) and superoxide dismutase( SOD) were analyzed. Immu-nohistochemical method was performed to detect the protein expression of p38MAPK and ERK. Western blot method was used to detect lung phosphorylated p38 MAPK ( p-p38 MAPK ) and pERK protein expres-sion changes. Result In the control groups, lung tis-sue showed a normal structure and clear pulmonary al-veoli under a light microscope. In the model group, ARDS characters such as extensive thickening of the alveolar wall, significant infiltration of inflammatory cells, demolished structure of pulmonary alveoli, and hemorrhage were found. In the all UTI treatment groups, these pathological changes in lung were markedly alleviated compared with those of LPS-in-duced ARDS group. Compared with control groups, lung W/D ratio, tumor necrosis factor-a ( TNF-α) , in-terleukin-18 ( IL-18 ) and surfactant protein A ( SPA ) in plasma ,and lung MDA,NO levels in lung homogenates in the LPS group were increased significantly, while the lung SOD levels in the LPS group were decreased. Compared with the LPS group, lung W/D ratio, TNF-aIL-18 and ( SPAin plasma , and lung MDA levels in lung homogenates in the UTI groups were decreased significantly, while the lung SOD levels in the UTI groups were increased. Immunohistochemistry showed that positive expressions of p38 MAPK and ERK in cy-toplasm and nucleus in the ulinastatin treatment groups were significantly lower than those in the model group. Western blot showed that compared with the control group, the p-p38MAPK and pERK protein expression in LPS group were significantly increased, and the uli-nastatin could inhibit the protein expressions compared with model group. Conclusion Ulinastatin can signifi-cantly ameliorate the lung injury induced by LPS in rats via the intervention of p38 MAPK and ERK signa-ling pathway and reducing inflammation and antioxidant effect.
3.Troglitazone reduces the inhibitory effect of sirolimus on premature 3T3-L1 cell's function
Jinhong LI ; Hang LI ; Yingjiu LIU ; Guojuan ZHANG ; Hongchao YIN
Chinese Journal of Nephrology 2012;28(4):296-300
Objective To investigate the effects of troglitazone on cholesterol homeostasis and secretion of 3T3-L1 cells by sirolimus and the underlying mechanisms. Methods In vitro cultured 3T3-L1 cells were divided into control group,sirolimus (100 nmol/L) group,sirolimus(100nmol/L)+ troglitazone (10 μmol/L) group and troglitazone (10 μmol/L) group.High performance liquid chromatography (HPLC) was used to measure intracellular cholesterol accumulation.ELISA was used to measure leptin excretion.Quantitative real-time PCR and Western blotting were used to examine mRNA and protein expression of PPARγ. Results Free cholesterol of sirolimus +troglitazone group was 1.19 times of sirolimus group (P<0.05).The leptin secretion levels of control group,sirolimus group,sirolimus+troglitazone group and troglitazone group were (19.02±0.52) μg/L,(15.62±0.47) μg/L,(16.45±0.51) μg/L,(18.07±0.66) μg/L,respectively.And the leptin secretion level of sirolimus+ troglitazone group was 1.05 times of sirolimus group (P<0.05).The PPARγmRNA expressions of sirolinus group,sirolimus + troglitazone group and troglitazone group were 0.60±0.14,1.12±0.27,1.30±:0.14 folds of control,and the PPARγ mRNA expression of sirolimus + troglitazone group was higher than that of sirolimus group (P<0.05).PPARγ protein expression had the same tendency. Conclusion Troglitazone reduces the inhibitory effect of sirolimus on PPARγ transactivation and the inhibitory effect of sirolimus on 3T3-L1 cells differentiation and adipogenesis.
4.Effects of sodium ferulute on experimental arrhythmias
Ping LI ; Qioutang ZENG ; Hongmei QIOU ; Guiyuan WANG ; Guojuan ZHANG ;
Chinese Pharmacological Bulletin 1987;0(03):-
AIM To study effect of sodium ferulute on experimental arrhythmias. METHODS Arrhythmias were induces by drugs and myocardial ischemia. RESULTS Sodium ferulute 0 6 g?kg -1 iv antagonized arrhythmias induced by ouabain, adrenalin and myocardial ischemia( P
5.Enhanced uptake of human mesangial cell line to oxidized low density lipoprotein stimulated by interleukin-1β partly through the lectin-like oxidized low-density lipoprotein receptor pathway
Hua LIU ; Hang LI ; Jianling TAO ; Yubing WEN ; Guojuan ZHANG ; Xuewang LI
Chinese Journal of Nephrology 2010;26(7):520-524
Objective To analysis if intedeukin-1β (IL-1β) can regulate human mesangial cells (HMC) to uptake oxidized low density lipoprotein (Ox-LDL) and if the effect of IL-lβ be changed through the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-l)pathway. Methods The uptake of HMC to Ox-LDL stimulated by IL-1β was observed using Oil Red "O" and flow cytometry. The level of LOX-1 in HMC induced by IL-1β and Ox-LDL was examined using real-time PCR and Western blotting. Results Uptake of Ox-LDL and Dil-Ox-LDL by HMC was up-regulated upon stimulation with IL-1β in a dose- and time-dependent manner. Intracellular mean fluorescence density of Dil-Ox-LDL with LOX-1 blocker in IL-1β stimulation group was decreased compared to that without blocker. The peak level of LOX-1 mRNA reached after 6 h of stimulation and was as high as 6.87-fold of control. IL-1β could induce LOX-1 mRNA expression in a dose-dependent manner. Treated with 10 μg/L IL-1β for 12 h, the upregulation effect on LOX-1 mRNA was as high as 6.57-fold of control. IL-1β could induce LOX-1 protein expression in a time- and dose-dependent manner. The peak level of LOX-1 protein reached after 24 h of stimulation of 5 μg/L IL-1β and was as high as 1.88-fold of control. Treated with 10 μg/L IL-1β for 24 h, the up-regulation effect on LOX-1 protein reached peak and was as high as 2.57-fold of control. IL-1β could induce LOX-1 mRNA and protein expression in a dosedependent manner. Conclusion The expression of LOX-1 can be up-regulated by IL-1β in a dose-dependent manner and the enhanced uptake of HMC to Ox-LDL stimulated by IL-1β partly through the LOX-1 pathway, which means the dyslipidemia of HMC can be enhanced by inflammatory cytokines.
6.Preliminary Research on Dynamic Optical Breast Imaging in Breast Cancer
Guojuan TAN ; Jie WANG ; Cui LIU ; Chunmian LI ; Zhang JOHN ; Weiping WANG
Chinese Journal of Medical Imaging 2010;(1):93-95
Purpose A new way in breast cancer detection, Dynamic Optical Breast Imaging (DOBI) was studied. Materials and Methods 52 patients receiving breast biopsy and DOBI were enrolled in this study. 19 were proved of breast cancer, 33 were benign. Results 94.8% of blue area in non-breast cancer lesions was found as wandering or diffusive pattern, while 68.42% breast cancer showed focal pattern. 86.46% of the curve signature of blue area in non-breast cancer lesions was wavy or flat, while 57.37% of breast cancer showed a steep decline. In 64.58% non-breast cancer, the curve of blue area was similar to that of non-blue area. 78.95% breast cancer had their curve different from that of non-blue area. The absolute value of amplitude (-5.77±2.13) of blue area in cancer was higher than that in non-cancer ( -3.34±0.87). The differences were all statistically significant(P<0.05). Conclusion The spatial and temporal characteristics of DOBI were of diagnostic and differential value for breast cancer. The absolute value of amplitude, over|-5|, also helped the diagnosis of breast cancer.
7.MicroRNA-mediated Tumor Multidrug Resistance and Function of Traditional Chinese Medicine
Ruijuan ZHANG ; Jianhua XU ; Wenyan YU ; Guojuan WANG ; Jue SUN ; Zhongze FAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(7):1515-1520
MicroRNA (miRNA for short) can induce mRNA cleavage or inhibit mRNA translation and regulate gene expression in the post-transcriptional level, which involves cell development, proliferation, differentiation, apoptosis, and a series of important biological processes. Recent studies have found that the abnormal regulation of miRNA's target genes may be involved in tumor resistance. And it is expected to become important tumor resistance-associat-ed molecular markers and therapeutic targets. Mechanism of traditional Chinese medicine (TCM) and its active ingre-dients can affect miRNA to regulate target proteins and target genes mediated tumor multidrug resistance. It can pro-vide new ideas for the mechanism of reversing multidrug resistance by TCM.
8.Relationship between Diabetic Retinopathy and Peripheral Arterial Disease in Type 2 Diabetes Patients
Danqiao ZHANG ; Yiqin QI ; Wanting FENG ; Chuan YANG ; Chuan WANG ; Kan SUN ; Guojuan LAO ; Li YAN ; Meng REN
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(5):732-737
[Objective]To explore the relationship between peripheral arterial disease(PAD)and diabetic retinopathy(DR)in type 2 diabetes patients.[Methods]A total of 99 patients diagnosed with PAD were classified into grade 1-3 by their total scores of peripheral arterial stenosis assessed by color doppler ultrasound examinations,where the degree of stenosis 30% ~ 49% scored 0, 50%~99%scored 1,lumen occlusion(i.e. degree of stenosis 100%)scored 2,and therefore the total score 0-2 was categorized into Grade 1 ,3~4 into Grade 2 ,5~12 into Grade 3. The bilateral anterior tibial artery ,posterior tibial artery and dorsalis pedis artery of these patients were analyzed. The presence of diabetic retinopathy(DR)was graded from retinal photographs using a standard protocol.[Results]Among 99 cases of type 2 diabetic patients with peripheral arterial disease ,58.6%of them were male with average age of 67.3 ± 7.9 years old. Patients of Grade 1,Grade2,Grade 3 lesion accounted for 45.4%,30.3%,24.2%,respectively. Age, gender,smoking history,SBP,DBP,BMI,FBG,TC,TG,LDL-C,HDL-C,HbA1C among 3 groups were not statistically signifi-cant. The associations of DM duration and HbA1C value were significantly larger in DR than in PAD. The proportion of DR patients increased with the severity degree of PAD(p for trend=0.004). Degree of stenosis Grade 2 and Grade 3 could be predictive for DR.[Conclusions]DR is associated with the severity degree of PAD in type 2 diabetes patients as evaluated by duplex ultrasonography.Degree of stenosis Grade 2 and 3 could be used for screening or finding DR. Strategies for optimum treatment and early prevention are needed.
9.Clinical value of neutrophil to lymphocyte ratio in maintenance hemodialysis patients
Xiuji LI ; Guojuan ZHANG ; Jie ZHENG ; Wei CHEN ; Wen HUANG
Chinese Journal of General Practitioners 2018;17(6):457-461
Objective To investigate the clinical value of neutrophil to lymphocyte ratio (NLR) in evaluation of inflammation and prediction of cardiovascular events in maintenance hemodialysis (MHD) patients.Methods One hundred and eight stable MHD patients were recruited from Dialysis Center of Beijing Tongren Hospital from October 2015 to December 2015.The general information,complete blood count,hsCRP,biochemical test,iron metabolic indicators,pre-dialytic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.MHD patients were divided into the low NLR group and high NLR group according to the median of NLR (2.82).All patients were followed up for 18 months,cardiovascular events (CVE) were recorded during this period.Results In the high NLR group the dialysis vintage,white blood cell count,neutrophil count,NLR and hsCRP were significantly higher than those in the low NLR group [(88.0 ± 50.4) vs.(62.4 ± 40.6) months (t =2.48,P =0.02),(6.96 ± 1.82) × 109/L vs.(5.83 ± 1.33) × 109/L(t =3.14,P=0.00),(4.94 ± 1.38) × 109/L vs.(3.36 ±0.87) × 109/ L(t=6.08,P=0.00),(4.16±1.25) vs.(2.15 ±0.46) points(t=9.48,P=0.00),(7.85±4.92) vs.(3.13 ± 2.23) mg/L (t =4.97,P =0.00)].In the high NLR group lymphocyte count and transferrin saturation were significantly lower than those in the low NLR group[(1.25 ± 0.40) × 109/L vs.(1.58 ± 0.34) ×109/L,t=3.97,P=0.00;(25.7±10.2)% vs.(32.6±17.2)%,t=2.17,P=0.03].There were no significant differences in age,sex,diabetes proportion,pre-dialytic SBP,pre-dialytic DBP,urea clearence index(Kt/V),hemoglobin,serum ferritin,serum calcium,serum phosphorus,intait parathyroid hormone,albumin,serum creatinine,carbon dioxide binding capacity and blood lipids between the two groups (P > 0.05).Bivariate correlation analysis showed that NLR was positively correlated with dialysis vintage and hsCRP (r =0.311,P =0.01;r =0.574,P =0.00);white blood cell count and neutrophil count were positively correlated with hsCRP (r =0.327,P =0.00;r =0.488,P =0.00).During follow-up period 9 cases of CVE (16.7%) and 20 cases of CVE (37.0%) occurred in the low NLR group and high NLR group,respectively (x2 =5.70,P =0.03).Cox regression analysis showed that age,NLR and serum phosphorus level were risk factors of CVE in MHD patients (HR =1.075,P =0.00,HR =1.646,P =0.00;HR =1.912,P =0.02).Conclusion NLR can predict inflammation and is one of the risk factors for CVE in MHD patients.
10.The effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor on migraine: a systematic review and meta-analysis
Xiaoxiao LIU ; Liqiong GUO ; Miao WANG ; Qinpeng WANG ; Yanju ZHANG ; Dandan SU ; Guojuan WANG ; Cheng LIANG
Chinese Journal of Neurology 2020;53(7):520-527
Objective:To evaluate the effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) on migraine.Methods:Database of PubMed, Embase, Cochrane, CNKI, Wangfang digital journals were searched for randomized controlled trials (RCTs) of CGRP-mAbs in treatment of migraine. Quality of enrolled literature was assessed by the software of Review Manager 5.3 and software of StataMP14 was employed to conduct meta analysis.Results:A total of 13 RCTs were included, including 6 218 adult migraine patients (experimental group: 2 679 patients, placebo group: 3 539 patients). Meta analysis suggested that CGRP-mAbs for preventive treatment of migraine significantly reduced the monthly migraine days from baseline (standardized mean difference (SMD)=-0.35, 95% CI-0.4--0.3) and monthly acute migraine-specific medication consumption from baseline (SMD=-0.38, 95% CI-0.43--0.32), as compared with placebo group. CGRP-mAbs for preventive treatment of migraine significantly increased the ≥50% reduction from baseline in migraine days per month ( RR=1.65, 95% CI 1.54-1.76). The adverse events were similar between the CGRP-mAbs group and placebo group ( RR=1.06, 95% CI 1.01-1.10). Conclusion:CGRP-mAbs are effective and safe for preventive treatment of migraine.