Effect of Coiquhoumia Root on the Expression of Transforming Growth Factor-β in Mesangiai Proliferation Giomerulonephritis Model

Summary： To study the efficacy and the mechanism of Colquhoumia root （ Tripterygium hypoglaucure （Le,vL） Hutch） in the treatment of mesangial proliferation glomerulonephritis （MsPGN）, SD rats were injected with anti-thymoeyte serum （ATS） to make MsPGN model （anti-Thyl model）. The rats were then divided into 3 groups： normal control group, anti-Thyl model group and treatment group. Histopathologieal （HE, PAS）, immunohistoehemieal, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β protein and mRNA in the tissues of kidney. Our result showed that proteinuria and the ratio of extraeellular matrix/glomerular capillaries area （ECM/CA） were increased significantly in model group. The expression of both TGF-β protein and mRNA in glomeruli was much higher in model group than in control group （P〈0.01）. After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.     

Effects of Biejia Ruangan Tablet(复方鳖甲软肝片)-Containing Serum on Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Expression in Cultured Renal Interstitial Fibroblasts

Objective:To investigate the effects of Biejia Ruangan Tablet(复方鳖甲软肝片方,BRT)- containing serum on the expression of matrix metalloproteinase(MMP-9) and tissue inhibitor of metalloproteinase(TIMP-1) in cultured renal interstitial fibroblasts.Methods:Different BRT-containing sera were prepared by gastric gavages to rats with the high-dose(7 g/kg),mid-dose(3.5 g/kg),and low-dose(1.75 g/kg)BRT respectively.The expression of extracellular matrix in NRK-49 F cells was induced by treatment with human transforming growth factor-β1(recombined human TGF-β1),and BRT-containing serum.Western blotting and Northern blotting were used to measure type Ⅰ and Ⅲ procollagen,MMP-9,and TIMP-1.Results:The high dose BRT-containing serum could decrease the type Ⅰ and Ⅲ procollagen gene expression which boosted by TGF- β1,at the same time cut down TIMP-1 protein and gene expression which increased by TGF- β1(P0.05).Treatment of cells with recombined human TGF- β 1 had no significant effect on MMP-9 expression and BRTcontaining serum also had no effect on MMP-9 expression.Conclusions:High dose BRT has anti-fibrosis effects in NRK-49 F cells,as indicated by its inhibition of type Ⅰ and Ⅲ procollagen and TIMP-1 expression.     

Xuezhikang(血脂康) Reduced Renal Cell Apoptosis in Streptozocin-Induced Diabetic Rats through Regulation of Bcl-2 Family

Objective: To investigate the effect of Xuezhikang(血脂康, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. Methods: Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK(1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion(UAE) measurement. Periodic acid-Schiff(PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling(TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C(Cyt C) and caspase-9 concentration were detected by Western blot. Results: Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months(P0.05 or P0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. Conclusions: Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.     

Effect of Quyu Chencuo Formula(去菀陈莝方)on Renal Fibrosis in Obstructive Nephropathy Rats

Objective: To observe the effect of Quyu Chencuo Formula(去菀陈莝方, QCF) on renal fibrosis in rats with obstructive nephropathy. Methods: Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction(UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital(50 mg/kg) anesthesia on the 14 th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin(HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor β1(TGF-β1), and real-time polymerase chain reaction(RT-PCR) was employed to examine the expressions of TGF-β1, α-smooth muscle actin(α-SMA) and E-cadherin mRNA. Results: HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-β1 expression was increased significantly in the model group, while decreased significantly in the QCF group(P0.05); RT-PCR showed that the mRNA expression of α-SMA and TGF-β1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group(P0.05). The mRNA expression of E-cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group(P0.05). Conclusion: QCF may improve renal fibrosis by regulating the expressions of TGF-β1, α-SMA and E-cadherin, and prevent the progress of kidney fibrosis.     

Fuzheng Huayu Formula(扶正化瘀方) Prevents Rat Renal Interstitial Fibrosis Induced by HgCl_2 via Antioxidative Stress and Down-regulation of Nuclear Factor-Kappa B Activity

Objective:To investigate the mechanism of action of Fuzheng Huayu Formula(扶正化瘀方,FZHY)against renal interstitial fibrosis(RIF)relating to oxidative injury and nuclear factor-kappa B(NF-κB)activity.Methods:Thirty-two Sprague-Dawley rats were randomly divided into 3 groups:normal group,model group and FZHY treatment group.The RIF model was induced by oral administration of HgC l2 at a dose of 8 mg/kg body weight once a day for 9 weeks.Meanwhile,rats in FZHY treatment group orally took FZHY at a dose of4.0 g/kg rat weight for 9 weeks.The content of hydroxyproline(Hyp)and collagen deposition in kidney were observed.The activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),the content of glutathione(GSH)and malondialdehyde(MDA)of kidney were tested.The expressions of inhibitor-κappa B(IκB),phospho-IκB(p-IκB),tumor necrosis factor-α(TNF-α),matrix metalloproteinase-2(MMP-2)andα-smooth muscle actin(α-SMA)were analyzed by Western blot.α-SMA expression was also observed by immunofluorescent staining.MMP-2 activity was measured by gelatin zymography.NF-κB activation was determined by electrophoretic mobility shift assay.Results:Renal interstitial fibrosis was induced by Hg Cl2,demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney(P0.01).FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the Hg Cl2-treated rats(P0.01).GSH content decreased obviously,and MDA content increased significantly in HgC l2-treated rats compared with that of normal rats(P0.01).FZHY significantly increased GSH content and decreased MDA content in the model rats(P0.01).The expressionα-SMA was increased in model rats compared with that of normal rats,FZHY significantly decreased its expression(P0.01).The expressions of p-IκB and TNF-αand MMP-2,MMP-2 activity,and NF-κB activation were increased in model group compared with that in normal group(P0.01),FZHY significantly decreased NF-κB activation,MMP-2 activity and p-IκB and TNF-αexpressions(P0.01).Conclusions:FZHY could protect kidney from oxidative injury intoxicated by Hg Cl2,and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney,these effects importantly contributed to FZHY action mechanism against renal interstitial fibrosis.     

Fuzheng Huayu Formula (扶正化瘀方) Prevents Rat Renal Interstitial Fibrosis Induced by HgCl2 via Antioxidative Stress and Down-regulation of Nuclear Factor-Kappa B Activity

Objective: To investigate the mechanism of action of Fuzheng Huayu Formula (扶正化瘀方, FZHY) against renal interstitial fibrosis (RIF) relating to oxidative injury and nuclear factor-kappa B (NF-κB) activity. Methods: Thirty-two Sprague-Dawley rats were randomly divided into 3 groups: normal group, model group and FZHY treatment group. The RIF model was induced by oral administration of HgCl2 at a dose of 8 mg/kg body weight once a day for 9 weeks. Meanwhile, rats in FZHY treatment group orally took FZHY at a dose of 4.0 g/kg rat weight for 9 weeks. The content of hydroxyproline (Hyp) and collagen deposition in kidney were observed. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of glutathione (GSH) and malondialdehyde (MDA) of kidney were tested. The expressions of inhibitor-κappa B (IκB), phospho-IκB (p-IκB), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) were analyzed by Western blot. α-SMA expression was also observed by immunofluorescent staining. MMP-2 activity was measured by gelatin zymography. NF-κB activation was determined by electrophoretic mobility shift assay. Results: Renal interstitial fibrosis was induced by HgCl2, demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney (P<0.01). FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the HgCl2-treated rats (P<0.01). GSH content decreased obviously, and MDA content increased significantly in HgCl2-treated rats compared with that of normal rats (P<0.01). FZHY significantly increased GSH content and decreased MDA content in the model rats (P<0.01). The expression α-SMA was increased in model rats compared with that of normal rats, FZHY significantly decreased its expression (P<0.01). The expressions of p-IκB and TNF-α and MMP-2, MMP-2 activity, and NF-κB activation were increased in model group compared with that in normal group (P<0.01), FZHY significantly decreased NF-κB activation, MMP-2 activity and p-IκB and TNF-α expressions (P<0.01). Conclusions: FZHY could protect kidney from oxidative injury intoxicated by HgCl2, and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney, these effects importantly contributed to FZHY action mechanism against renal interstitial fibrosis.     

尾加压素Ⅱ和转化生长因子β1在糖尿病大鼠肾脏的表达及其意义

目的：观察尾加压素Ⅱ（UⅡ）和转化生长因子β1（TGF-β1）蛋白在糖尿病大鼠肾小管上皮细胞和肾小球的动态表达规律及其在糖尿病肾病发病中的作用。方法：30只雄性Wistar大鼠随机分为对照组及糖尿病2、4、8和12周组。糖尿病大鼠模型用单次腹腔注射链脲菌素（55 mg•kg^-1）诱发。生化法测定血糖、血和尿肌酐、尿白蛋白和尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）含量。免疫组织化学法检测肾脏UⅡ、TGF-β1、纤连蛋白（FN）和Ⅳ型胶原（Col Ⅳ）的表达。结果：糖尿病各组大鼠的生化指标均明显高于对照组（P<0.05）。糖尿病大鼠肾小管上皮细胞和肾小球可见UⅡ和TGF-β1阳性染色颗粒,对照组未见该阳性染色颗粒。与糖尿病2周时比较,糖尿病4、8和12周组UⅡ和TGF-β1表达（阳性染色肾小管数和细胞数）随着病程进展进行性增加(P<0.05),肾小管上皮细胞UⅡ的表达水平与尿NAG含量呈正相关（r=0.895,P<0.01）。糖尿病组大鼠肾小管上皮细胞UⅡ与TGF-β1的表达水平呈正相关（r=0.769,P<0.01）。糖尿病8和12周组大鼠肾脏FN和ColⅣ表达明显高于对照组（P<0.05）。结论：糖尿病大鼠肾小管上皮细胞和肾小球UⅡ及TGF-β1蛋白表达均明显增加,提示其在糖尿病肾病的肾小管损害及细胞外基质积聚中可能起一定作用。     

五味子提取物对糖尿病大鼠肾脏组织中基质金属蛋白酶表达的影响及其肾脏保护作用

目的：探讨五味子提取物对糖尿病大鼠肾脏组织中基质金属蛋白酶（MMPs）表达的影响,从基质降解角度阐明其肾脏保护作用。方法：采用链脲佐菌素（STZ）复制糖尿病大鼠模型,45只糖尿病模型大鼠随机分为模型组、五味子组和贝那普利组,每组15只;另取15只大鼠作为正常对照组。给药12周后检测各组大鼠常规血、尿生化指标及组织学改变;检测各组大鼠血清和肾组织匀浆中血糖（BG）、血尿素氮（BUN）、血肌酐（Scr）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（T-CHO）、甘油三酯（TG）水平和尿白蛋白、尿总蛋白排泄率;免疫组织化学法检测大鼠肾组织中纤维连接蛋白（FN）、Ⅳ型胶原蛋白（Col Ⅳ）、基质金属蛋白酶抑制剂2（TIMP-2）的表达量;酶谱法检测大鼠肾组织中MMP-2活性。结果：与模型组比较,五味子组大鼠肾小球系膜聚集等现象明显减轻,尿白蛋白排泄率、LDL-C及血清丙二醛（MDA）水平均明显降低（P<0.05）,肾组织中过氧化氢酶（CAT）（P<0.01）和超氧化物歧化酶（SOD）活性升高（P<0.05）,MDA水平降低（P<0.05）。免疫组织化学检测,与模型组比较,五味子组大鼠肾组织中FN、Col Ⅳ和TIMP-2表达量明显降低。酶谱法检测,与模型组比较,五味子组和贝那普利组大鼠肾组织中MMP-2活性明显升高（P<0.05）。结论：五味子提取物对STZ导致的实验性糖尿病大鼠的肾脏有保护作用,其机制可能与抑制氧化应激、提高MMP-2活性、抑制TIMP-2表达从而改善基质降解有关。     

N-乙酰半胱氨酸对糖尿病大鼠肾脏保护作用的研究

目的观察N-乙酰半胱氨酸(NAC)对糖尿病大鼠肾脏的保护作用,并探讨其作用机制。方法用免疫组化方法检测肾组织胶原Ⅳ、纤维连接蛋白(FN)的蛋白表达;用RT-PCR检测肾组织基质金属蛋白酶-9(MMP-9)及其组织抑制因子-1(TIMP-1)mRNA的表达。结果 NAC能减少尿蛋白,降低血肌酐水平,减少胶原Ⅳ、FN及TIMP-1mRNA的表达,增加MMP-9mRNA的表达。结论 NAC可能通过上调MMP-9在肾组织的表达,减轻细胞外基质(ECM)的聚积,起到减少尿蛋白排泄量,保护肾功能的作用。     

褐藻多糖硫酸酯对TGF-β1孵育的人肾小球系膜细胞MMP-2、TIMP-2表达的影响

目的观察褐藻多糖硫酸酯(Fucoidan FPS)对TGF-β1下刺激人肾小球系膜细胞MMP-2、TIMP-2分泌的影响,探讨其在慢性肾衰竭(Chronic Renal Failure CRF)防治中的意义。方法用TGF-β1作为刺激因子,孵育体外培养的人肾小球系膜细胞(Human Mesangial cell HMC),并分别用不同浓度的FPS干预,具体分组如下:模型组(TGF-β14 ng/ml)、FPS高剂量组(TGF-β14 ng/ml+FPS 100 ug/ml)、FPS中剂量组(TGF-β14 ng/ml+FPS 50 ug/ml)、FPS低剂量组(TGF-β14 ng/ml+FPS25 ug/ml)、FPS对照组(FPS 100ug/ml)、正常对照组。ELISA技术检测HMC培养上清液中MMP-2、TIMP-2蛋白表达水平,Re-altime PCR技术检测HMC的MMP-2、TIMP-2 mRNA表达水平。结果与正常对照组相比,TGF-β1能减少HMC的MMP-2蛋白及mRNA表达(P0.01),增加HMC的TIMP-2蛋白及mRNA表达(P0.01);FPS能阻断TGF-β1刺激下HMC的MMP-2蛋白及mRNA表达减少、TIMP-2蛋白及mRNA表达增加(P0.01,P0.05);FPS对照组与正常对照相比MMP-2、TIMP-2蛋白及mRNA表达差异无统计学意义(P0.05)。结论褐藻多糖硫酸酯能阻断TGF-β1刺激下人肾小球系膜细胞MMP-2、TIMP-2表达的比例失衡,阻断了由MMP-2、TIMP-2比例失衡导致的ECM积聚,从而延缓了慢性肾衰竭的进展。     

联合用药延缓阿霉素肾病大鼠肾间质纤维化的研究

目的：探讨贝那普利和蝙蝠蛾拟青酶Cs-4联合应用对阿霉素肾病模型大鼠肾纤维化的保护作用及调节机制。方法：将60只SD大鼠随机分为模型组（M组）、贝那普利组（B组）、联合治疗组（U组）3组,每组20只。8周后观察各组大鼠24h尿蛋白定量、血脂、血浆总蛋白（TP）、血浆白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)的水平及肾脏病理改变,免疫组化检测肾层粘连蛋白（LN）、肾组织中纤连蛋白(FN)、胶原蛋白Ⅳ(Col Ⅳ)、转化生长因子β1(TGF-β1)的表达,RT PCR方法测定肾皮质转化生长因子β1（TGF-β1）和纤溶酶原激活物抑制物（PAI-1）、组织性金属蛋白酶抑制物1(TIMP 1)mRNA的表达。结果：U组、B组分别和M组相比,24h尿蛋白定量、BUN、Scr、甘油三脂(TG)、总胆固醇(Cho)明显降低（P＜0.01）,TP和ALB明显升高（P＜0.01）,U组和B组相比,BUN、Scr、TG、Cho亦明显降低（P＜0.05）;M组肾脏病理肾间质纤维化较重,而B组较轻,U组最轻;免疫组化可见B组和U组中LN、FN、Col Ⅳ、TGF-β1的表达明显低于M组（P＜0.01）,并且U组和B组相比,Col Ⅳ、TGF-β1的表达明显降低（P＜0.05）;RT PCR显示B组、U组TGF-1mRNA、PAI-1mRNA、TIMP-1mRNA的表达,均较M组降低（P＜0.01）,U组较B组亦明显降低（P＜0.05）。结论：蝙蝠蛾拟青酶Cs-4和贝那普利联合应用有相加作用,能有效的延缓肾间质纤维化。     

MMP-1、TIMP-1及TGF-β1在风湿性心脏病瓣膜组织中的 表达及意义

目的 探讨基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶组织抑制剂-1（TIMP-1）及转化生长因子-β1（TGF-β1）在风湿性心脏病（RHD）瓣膜组织中的表达及意义。方法 采用Western blot及RT-PCR法检测RHD瓣膜组织（实验组, n=30）及无RHD瓣膜组织（对照组, n=15）中MMP-1、TIMP-1及TGF-β1蛋白与mRNA的表达,碱水解法检测胶原代谢情况,Masson法进行胶原纤维染色并检测胶原容积分数（CVF）。分析MMP-1、TIMP-1及TGF-β1与CVF的相关性。结果 MMP-1及TGF-β1蛋白和mRNA在实验组中的表达高于对照组,而TIMP-1蛋白和mRNA在实验组中的表达低于对照组,差异有统计学意义( P<0.05)。实验组胶原含量及CVF均高于对照组( P<0.05)。相关性分析显示,MMP-1与TGF-β1呈正相关,TIMP-1与TGF-β1呈负相关,MMP-1及TGF-β1与CVF呈正相关,TIMP-1与CVF呈负相关。结论 MMP-1、TGF-β1和TIMP-1参与了RHD瓣膜病变的纤维化进展。     

BMP-7拮抗系膜细胞TGF-β1诱导MMPs的表达

目的 观察骨形态发生蛋白-7(bone morphogenetic protein-7,BMP-7)对转化生长因子-β1 (transforming growth factor-β1,TGF-β1)诱导系膜细胞表达基质金属蛋白酶(matrix metalloprotease,MMP)2、9的影响.方法 将体外培养系膜细...     

缬沙坦对单侧输尿管梗阻大鼠肾间质纤维化的影响

目的探讨血管紧张素ⅡⅠ型受体拮抗剂(AT1RA)缬沙坦对单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的影响及其可能机制。方法35只SD大鼠随机分为假手术组、模型组和缬沙坦组(n=10),建立大鼠UUO模型,于术后4周检测血清肌酐(SCr)、血尿素氮(BUN)、血浆血管紧张素Ⅱ(AngⅡ),尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG);取梗阻侧肾组织,以H-E、Masson染色观察肾小管间质病变,免疫组织化学染色观察α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)、纤溶酶原激活物抑制剂1(PAI-1)、转化生长因子β1(TGF-β1)及肝细胞生长因子(HGF)在肾间质的阳性染色,并进行半定量分析。结果与假手术组相比,模型组大鼠SCr、BUN、血浆AngⅡ,尿NAG、β2-MG水平以及α-SMA、FN、PAI-1、TGF-β1表达均显著升高(P<0.01)。与模型组相比,缬沙坦组大鼠SCr、BUN,尿NAG及β2-MG水平差异无统计学意义(P>0.05),但血浆AngⅡ及肾间质α-SMA、FN、PAI-1、TGF-β1表达均显著降低,HGF表达则显著增高(P<0.01)...     

疏血通注射液对糖尿病大鼠肾脏TGF-β_1及Col-Ⅳ表达的影响

目的:探讨疏血通注射液对实验性糖尿病大鼠尿蛋白和转化生长因子β_1(Transforming growthfactor β_1,TGF-β_1)、Ⅳ型胶原(Cofiegen type Ⅳ,Col-Ⅳ)表达的影响.方法:采用链脲佐菌素(Streptozotocin,STZ)制备早期糖尿病肾病(Diabetic nephropathy,DN)模型,随机分为正常对照组、DN未治疗组、疏血通治疗组、苯那普利对照组,8周后观察尿白蛋白排泄率(Urinary albumin excretion rate,UAER)、尿β_2微球蛋白(β_2-miro globulin,β_2-MA)、肾脏肥大指数(KW/BW)的变化;免疫组化法检测肾组织TGF-β_1、Col-Ⅳ的表达水平.结果:与DN未治疗组相比,疏血通组的UAER、尿β_2-MA、KW/BW均下降(P＜0.05或P＜O.01),肾组织TGF-β_1、Col-Ⅳ表达下调(P＜0.05).结论:疏血通注射液对糖尿病大鼠具有肾脏保护作用,其机制可能与下调肾组织TGF-β1、Col-Ⅳ的表达有关.     

非诺贝特对高糖培养肾小球系膜细胞胞外基质产生及降解影响

目的：探讨非诺贝特对糖尿病肾病的保护机制。方法：大鼠肾小球系膜细胞分别培养在正常糖浓度（5.5 mmol.L-1,对照组）、高糖浓度（25 mmol.L-1,高糖组）及25 mmol.L-1葡萄糖＋非诺贝特100μmol.L-1（非诺贝特组）。CCK-8测定系膜细胞增殖;ELISA法检测培养上清液Ⅳ型胶原（Col-Ⅳ）、纤维连接蛋白（FN）、转化生长因子-β1（TGF-β1）、基质金属蛋白酶组织抑制因子-1（TIMP-1）;明胶酶谱法检测培养上清基质金属蛋白酶-2,9（MMP-2,9）的活性。结果：高糖组系膜细胞较对照组出现增殖增加,合成基质蛋白Col-Ⅳ,FN增多,MMP-2及MMP-9活性下降,TIMP-1含量增加,TGF-β1分泌增加。与高糖组比较非诺贝特干预后能完全或部分逆转上述变化。结论：非诺贝特能抑制高糖培养的系膜细胞增殖,减少胞外基质合成,增加胞外基质的降解。