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[摘要]
目的 观察丹参多酚酸盐对阳离子化牛血清白蛋白致膜性肾病大鼠血液生化指标、肾组织病理形态及足细胞裂孔隔膜蛋白CD2相关蛋白(CD2AP)、结蛋白(Desmin)表达的影响,探讨丹参多酚酸盐对膜性肾病大鼠的肾保护作用及其可能机制。方法 健康雄性SD大鼠随机分为对照组和造模组,采用尾iv阳离子化牛血清白蛋白的方法复制膜性肾病大鼠模型。造模成功的大鼠随机分为模型组、盐酸贝那普利组和丹参多酚酸盐低、中、高剂量(16.7、33.3、66.7 mg/kg)组。每组按相应剂量给药,给药结束后检测大鼠24 h尿蛋白定量(UTP)和血清总胆固醇(TC)、三酰甘油(TG)、总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)水平;免疫荧光、光镜、电镜下观察大鼠肾脏病理形态;免疫组化及实时荧光定量PCR(qRT-PCR)法检测各组大鼠肾组织CD2AP、Desmin mRNA的表达情况。结果 与对照组比较,模型组大鼠UTP显著增加(P<0.01),血清TC、TG水平显著升高(P<0.01),血清TP、ALB水平显著降低(P<0.01)。与模型组比较,各治疗组大鼠UTP、TC、TG水平均显著降低(P<0.05、0.01),TP、ALB水平均显著升高(P<0.01);丹参多酚酸盐各剂量组与盐酸贝那普利组大鼠UTP、TC、TG、TP、ALB比较无显著差异;丹参多酚酸盐各剂量组组内比较亦无明显差异。各组大鼠BUN、Scr相比无明显差异。与对照组比较,模型组大鼠肾组织CD2AP蛋白及mRNA表达量均显著减少,Desmin蛋白及mRNA表达量显著增多(P<0.01);与模型组比较,各治疗组大鼠CD2AP蛋白及mRNA表达量显著增多,Desmin蛋白及mRNA表达量显著减少(P<0.01);各治疗组之间相比无显著差异。结论 丹参多酚酸盐对膜性肾病大鼠的肾保护作用可能与上调CD2AP表达、下调Desmin表达,抑制足细胞损伤,保护肾小球滤过屏障的完整性有关。
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[Abstract]
Objective To observe the effects of salvianolate on blood biochemical indexes, pathological changes of renal tissue and expression of CD2AP and Desmin protein in membranous nephropathy rats induced by cationic bovine serum albumin. And to explore the renal protective effect of salvianolate on membranous nephropathy rats and its possible mechanism. Methods Healthy male SD rats were randomly divided into normal group and modle group. Rat models of membranous nephropathy were reproduced by injection of cationized bovine serum albumin through tail vein. Model successful rats were randomly divided into model group, benazepril group, and salvianolate groups (16.7, 33.3, and 66.7 mg/kg). Each group was given the dose of the corresponding drugs. After treatment, the level of 24 h urine total protein (UTP), serum total cholesterol (TC), triglyceride (TG), total protein (TP), albumin (ALB), urea nitrogen (BUN), and serum creatinine (Scr) were detected. Immunofluorescence, light microscope, and electron microscope were used to observe the pathological changes of rat kidney. Immunohistochemistry and real-time PCR were used to detect the expression of CD2AP and Desmin. Results Compared with the control group, levels of UTP, TC, and TG increased significantly (P < 0.01), levels of serum TP and ALB decreased significantly (P < 0.01) in the model group. Compared with the model group, the UTP, TC, and TG of each treatment group were significantly decreased (P < 0.05, 0.01), while the TP and ALB were significantly increased (P < 0.01). There was no significant difference in the UTP, TC, TG, TP, and ALB among each dosage of salvianolate and benazepril group. And there was no significant difference among each dose group of salvianolate. There was no significant difference among each groups in the level of BUN and Scr. Compared with the normal group, the expression of CD2AP in model group was significantly decreased and Desmin was significantly increased (P < 0.01). Compared with the model group, the expression of CD2AP increased and Desmin decreased in each treatment group (P < 0.01), but there was no difference among the treatment groups. Conclusion Salvianolate has kidney protective effect on membranous nephropathy rats. The mechanism may be related to up-regulating the expression of CD2AP, down-regulating the expression of Desmin, inhibiting podocyte injury and protecting the integrity of the glomerular filtration barrier.
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