缬沙坦抑制树突状细胞浸润改善单侧输尿管梗阻大鼠肾纤维化实验研究  

Effect of valsartan on renal fibrosis in unilateral ureteral obstruction rats by inhibiting dendritic cell infiltration

作　　者：高婷婷 刘颖[1] 郝秀英 郭阳 马英桓 GAO Ting-ting;LIU Ying;HAO Xiu-ying;GUO Yang;MA Ying-huan(Department of Cardiovascular Medicine,Air Force Hospital of People’s Liberation Army Northern Theater Command,Shenyang 110042,Liaoning Province,China)

机构地区：[1]中国人民解放军北部战区空军医院心血管内科,辽宁沈阳110042

出　　处：《中国临床药理学杂志》2021年第9期1091-1093,1106,共4页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省自然科学基金计划重点基金资助项目(20180530012)。

摘　　要：目的研究缬沙坦对单侧输尿管梗阻(UUO)大鼠肾纤维化的抑制作用。方法通过单侧输尿管结扎术建立大鼠UUO模型,随机分为假手术组、模型组和实验组,每组10只。假手术组只分离左侧输尿管但不结扎。实验组给予缬沙坦80 mg·d^(-1),假手术组与模型组灌胃等量生理盐水,干预4周。以苏木精-伊红(HE)和Masson染色观察大鼠肾组织中间质性胶原的沉积;以免疫组化方法检测单核细胞趋化因子-1(MCP-1)、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(vimentin)及E-cadherin纤维化相关蛋白的沉积情况;以免疫荧光方法检测CD1a^(+)CD80^(+)DC树突状细胞浸润情况。结果假手术组、模型组及实验组大鼠肾组织胶原分布情况分布为3.91±0.91,25.34±4.46,9.48±0.81;E-cadherin水平分别为116.54±13.83,18.11±9.36,60.23±0.67;MCP-1水平分别为25.18±1.64,97.70±25.74,61.93±11.51;TGF-β1水平分别为8.67±0.83,110.30±5.01,37.01±5.67;Viment水平分别为11.89±2.52,101.81±12.45,32.89±5.38;CD1a^(+)CD80^(+)DCs分布分别为458.25±90.24,2972.92±538.06,1363.59±183.31。与假手术组相比,模型组大鼠胶原沉积、肾纤维化相关蛋白及树突状细胞浸润程度均显著升高,且实验组低于模型组(均P<0.05)。结论缬沙坦可明显降低UUO后大鼠肾间质胶原的沉积,降低肾纤维化相关蛋白表达水平,可能通过阻抑DCs肾内迁移成熟,抑制免疫细胞介导的炎症反应。Objective To study the inhibitory effect of Valsartan on renal fibrosis in unilateral ureteral obstruction(UUO) rats. Methods UUO rat models were established by unilateral ureteral ligation and were randomly divided into sham-operation group, model group and experimental group with 10 rats in each group. In sham operation group, only the left ureter was separated but not ligated. Experimental group was given valsartan 80 mg·d^(-1), sham-operation group and model group were given the same amount of normal saline intragastrically for 4 weeks. The deposition of interstitial collagen in rat kidney was observed by HE and Masson staining. The deposition of monocyte chemotactic protein-1(MCP-1), transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), Vimentin and E-cadherin fibrosis-related proteins were detected by immunohistochemistry. The infiltration of CD1 a^(+)CD80^(+)dendritic cell was detected by immunofluorescence. Results The distribution of collagen were3. 91 ± 0. 91,25. 34 ± 4. 46,9. 48 ± 0. 81,E-cadherin level were 116. 54 ± 13. 83,18. 11 ± 9. 36,60. 23 ± 0. 67,MCP-1 level were 25. 18 ± 1. 64,97. 70 ± 25. 74,61. 93 ± 11. 51;TGF-1 levels were 8. 67 ± 0. 83,110. 30 ± 5. 01,37. 01 ± 5. 67;Viment levels were 11. 89 ± 2. 52,101. 81 ± 12. 45,32. 89 ± 5. 38,the distribution of CD1 a^(+)CD80^(+)DCs were 458. 25 ± 90. 24,2972. 92 ± 538. 06 and 1363. 59 ± 183. 31,respectively. Compared with sham-operation group,collagen deposition,renal fibrosis-associated protein and dendritic cells were significantly increased in model group,and were lower in experimental group than those in model group( P < 0. 05). Conclusion Valsartan can decrease the collagen deposition and the expression of renal fibrosis related protein in UUO rats,which may inhibit the migration and maturation of DCs in kidney and inhibit the inflammatory reaction mediated by immune cells.

关 键 词：缬沙坦 树突状细胞 慢性肾间质纤维化 

分 类 号：R97[医药卫生—药品]