首页> 中文期刊> 《中国中西医结合肾病杂志》 >连黄降浊颗粒对SHR肾组织VEGF和足细胞podocalyxin表达的影响

连黄降浊颗粒对SHR肾组织VEGF和足细胞podocalyxin表达的影响

         

摘要

Objective:To study the effects of Lianhuang Turbid Clearance Granules ( LHTCG) on VEGF and PCX expres-sions of kidney in SHR with unilateral nephrectomy. Methods:40 SHR of 10W male were randomly divided into five groups:the SHR group, the western medicine control group, the traditional Chinese medicine control group, the low dose group of LHTCG ( low dose group) and the high dose group of LHTCG ( high dose group) , the same week old Wistar-Kyoto rats ( WKY) were used as normal blood pressure ( BP) control group. All rats were removed of the right kidney. Medicines were given to each group according to the designed concentration and dosage. Urine mAlb,β2 -MG,α1 -MG, mAlb/Ucr, and BP of rats were measured at 8 weeks. All rats were anesthetized and sacrificed. Scr, Cys-C were measured by the blood samples, the left renal tissues were examined by HE stain, PAS stain and Masson stain. The changes of glomerular and tubular interstitial pathology were detected by light microscope. The chan-ges of glomerular capillary basement membrane and podocyte in kidney were detected by electron microscope. The protein expression of VEGF、PCX in kidney were observed by the immunohistochemistry, reverse transcription PCR and Western blotting. Results:Com-pared with the WKY group, mAlb,β2 -MG,α1 -MG, mAlb/Ucr, Scr, and Cys-C of the SHR group were increased and BP were elevated (P<0. 01), the four treatment group were lower than the SHR group (P<0. 05~0. 01), the high dose group were Signifi-cantly decreased than the other treatment group (P<0. 05~0. 01). Compared with the model group and control group, optical micro-scope showed that kidney and vessel pathological damage of rats were lessened by LHTCG. Compared with the other groups, the thick-ening of glomerular basement membrane and the fusion of podocyte foot processes were reduced by LHTCG with dose dependent. Im-munohistochemical, RT-PCR and Western blotting showed that:the protein expression of VEGF were down-regulated by LHTCG in the renal tissue of the high dose group, while the protein expression of PCX were up-regulated. Conclusion:Through foot process fu-sion reducing, proteinuria decreasing, up-regulation of PCX and the down-regulation of VEGF protein expression in unilateral ne-phrectomy SHR;glomerulosclerosis and interstitial fluid were ameliorated;the renal function was improved by LHTCG.%目的:观察连黄降浊颗粒对单侧肾切除SHR肾组织血管内皮细胞生长因子(VEGF)和足细胞podocalyxin(PCX)表达的影响.方法:40只SHR随机分为模型组(SHR组)、西药对照组(西药组)、中药对照组(中药组)、连黄降浊颗粒低剂量组(低剂量组)、连黄降浊颗粒高剂量组(高剂量组),6只同周龄WKY作为正常血压对照组(WKY组).右肾切除法建立高血压性肾损害动物模型.造模后各组给予相应药物,给药8周末测量血压,收集尿液观察尿微量白蛋白(mAlb)、β2-微球蛋白(β2-MG)、α1-微球蛋白(α1-MG)、尿微量白蛋白/尿肌酐(mAlb/Ucr);取血检测血肌酐(Scr)、血清胱抑素C(Cys-C).8周后处死所有大鼠,肾组织行HE、PAS和Masson染色,光镜观察肾小球和肾小管-间质病理变化;电镜观察肾脏毛细血管基底膜(GBM)及足细胞的变化;免疫组化、Western blotting和RT-PCR检测VEGF、PCX及PCX-mRNA表达水平.结果:给药第8周WKY组和4个治疗组血压显著低于SHR组(P<0.05~0.01),且4个治疗组血压差异亦有统计学意义(P<0.05).SHR组尿mAlb、β2-MG、α1-MG、mAlb/Ucr,血Scr、Cys-C明显高于WKY组(P<0.01),高剂量组显著低于其他治疗组(P<0.05~0.01).光镜下PAS染色显示SHR组肾小球病变明显,肾小球硬化指数(GSI)显著高于WKY组(P<0.01),高剂量组GSI明显降低(P<0.05~0.01);HE染色、Masson染色显示SHR组肾小管间质轻度纤维化,肾间质纤维化指数(IF)显著高于WKY组(P<0.01),高剂量组IF显著降低(P<0.05~0.01).透射电镜下SHR组足细胞及GBM形态结构明显改变,高剂量组足细胞、GBM均无显著改变.免疫组化、RT-PCR、Western blotting结果显示4个治疗组VEGF均低于SHR组,高剂量组VEGF表达显著降低;SHR组PCX及其m-RNA表达显著低于WKY组,高剂量组表达明显高于中、西药组和低剂量组.结论:连黄降浊颗粒能够有效缓解足突融合、减少尿蛋白,降低VEGF表达、上调PCX表达水平,减轻肾小球及肾小管-间质病理改变.

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