目的　探讨瞬时受体电位阳离子通道蛋白6 ( TRPC6)在正常人、小鼠和大鼠肾组织及小鼠足细胞系(MPC5)的表达和分布，为研究TRPC6在肾脏的功能及其与足细胞分子间的关系奠定基础。方法　1. 应用免疫组织化学方法观察TRPC6在正常人、小鼠和大鼠肾组织及MPC5分布。2. 通过反转录酶-聚合酶链反应(RT-PCR)检测TRPC6在小鼠肾组织和MPC5表达。3. 应用免疫蛋白印迹检测TRPC6在正常人、小鼠和MPC5表达。结果　1. TRPC6在正常人肾小球呈弱表达，在肾小管和肾血管表达较强，在小鼠和大鼠主要沿肾小球毛细血管袢和系膜区分布，肾间质也有少许表达。TRPC6在MPC5的荧光染色为阳性，在分化态细胞主要分布于胞膜表面。2. 在小鼠肾组织及MPC5均检测到特异性TRPC6的PCR产物条带。3. 在正常人、小鼠肾组织及MPC5均检测到特异性的相对分子质量为106的TRPC6蛋白条带。结论　TRPC6在正常人、小鼠和大鼠肾小球均有表达，在mRNA及蛋白水平均证实MPC5能表达TRPC6，为从离子通道的角度利用MPC5探讨蛋白尿发生的分子机制奠定基础。

蛋白尿是肾脏疾病最常见的临床症状之一。近年来，Nephrin、Podocin、CD2AP和α2actinin24等重要足细胞结构蛋白和细胞骨架分子的确立，为肾小球性蛋白尿发生机制的研究提供了新的思路[ 1～5 ] 。然而，由于蛋白尿临床病理以及遗传背景的异质性，其发生机制尤其是分子机制仍未完全阐明。2005年，Winn和Reiser研究组又确定了一个导致家族性局灶节段性肾小球硬化( FSGS ) 的基因——TRPC6[ 6， 7 ] ，其编码蛋白瞬时受体电位阳离子通道蛋白( transient recep tor potential cation channel 6，TRPC6)是一个非选择性阳离子通道，新近发现其在足细胞也有表达，而且和裂孔隔膜分子Nephrin以及Podocin间存在相互作用，这一发现将足细胞结构蛋白和离子通道联系起来，丰富了足细胞分子网络，拓宽了对肾小球性蛋白尿发生机制的认识。因此，认识该基因、筛查可能存在的突变以及进一步研究该基因的功能将对探讨蛋白尿发生的分子机制以及防治蛋白尿具有新的意义。本文着重介绍TRPC6突变致家族性FSGS，同时对TRPC6在肾脏疾病领域的研究也作一概述。

The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis2related proteins Fas and FasL in the kidney of rats with adriamycin2induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/ kg), valsantan (20 mg/ kg), or benazepril (3 mg/ kg) plus valsantan (20 mg/ kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling ( TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect .

Nephrin, podocin, CD2AP, and a-actinin-4 are important podocyte proteins that help maintain the integrity of the slit diaphragm and prevent proteinuria. Studies have shown that angiotensin-converting enzyme inhibitors, glucocorticoids, and all-trans retinoic acid (ATRA) have antiproteinuric effects. However, it is still unclear whether these drugs, with different pharmacological mechanisms, lead to a reduction in proteinuria by changing the expression and distribution of these important podocyte proteins. In this study, changes in the expression and distribution of nephrin, podocin, CD2AP, and a-actinin-4 were dynamically detected in Adriamycin-induced nephrotic (ADR) rats treated with three different drugs: lisinopril, prednisone, and ATRA. Nephropathy was induced by an intravenous injection of Adriamycin. After Adriamycin injection, rats received lisinopril, prednisone, and ATRA treatment, respectively. Renal tissues were collected at Days 3, 7, 14, and 28. The distribution and the expression of messenger RNA and protein of nephrin, podocin, CD2AP, and a-actinin-4 were detected by indirect immunofluorescence, real-time polymerase chain reaction, and Western blotting, respectively. With the intervention of lisinopril, prednisone, and ATRA, changes in the expression of nephrin, podocin, and CD2AP were diverse, which was different from that detected in ADR rats. After lisinopril and prednisone intervention, podocin exhibited prominent earlier changes compared with those of nephrin and CD2AP, whereas CD2AP showed more prominent changes after ATRA intervention. There was no change in the expression of a-actinin-4 molecule. In summary, we conclude that the antiproteinuric effects of lisinopril, prednisone, and ATRA were achieved by changes in the expression and distribution of the important podocyte molecules nephrin, podocin, CD2AP, and a-actinin-4. The pattern in the change of podocyte molecules after lisinopril and prednisone intervention was similar, but the pattern in the change of podocyte molecules after ATRA intervention was different from that of lisinopril or prednisone intervention.