文章摘要
鲁科达,张冰冰,石承乾,等.消瘀泄浊饮对慢性环孢素肾病大鼠ACE2-Ang(1-7)-MAS轴相关组分表达的影响[J].浙江中医药大学学报,2020,44(5):407-414.
消瘀泄浊饮对慢性环孢素肾病大鼠ACE2-Ang(1-7)-MAS轴相关组分表达的影响
Effect of Xiaoyu Xiezhuo Drink on the Expression of ACE2-Ang(1-7)-MAS Axis Components in Rats with Chronic Cyclosporine Nephropathy
DOI:10.16466/j.issn1005-5509.2020.05.001
中文关键词: 消瘀泄浊饮  慢性环孢素肾病  ACE2  Ang(1-7)  MAS  Ⅳ型胶原  肾间质纤维化
英文关键词: Xiaoyu Xiezhuo Drink  chronic cyclosporine nephropathy  ACE2  Ang(1-7)  MAS  collagen Ⅳ  renal interstitial fibrosis
基金项目:
作者单位
鲁科达 浙江中医药大学附属第一医院 杭州 310006 
张冰冰 浙江中医药大学 
石承乾 浙江中医药大学附属第一医院 杭州 310006 
张培培 浙江中医药大学附属第一医院 杭州 310006 
叶黎青 浙江中医药大学附属第一医院 杭州 310006 
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中文摘要:
      [目的]观察消瘀泄浊饮对慢性环孢素肾病大鼠血管紧张素转化酶2-血管紧张素(1-7)[angiotensin converting enzyme 2-angiotensin(1-7),ACE2-Ang(1-7)]-MAS轴相关组分表达的影响。[方法] 40只雄性SD大鼠按随机数字表法分为空白对照组、模型组、消瘀泄浊饮组和贝那普利组,每组各10只。采用3mg·mL-1的环孢素A溶液灌胃及低盐饮食建模,灌胃4周后检测大鼠血肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)水平,并计算内生肌酐清除率(creatinine clearance rate,Ccr);以苏木精-伊红(hematoxylin-eosin,HE)染色、Masson染色观察大鼠肾组织病理学改变,免疫组化法检测肾组织ACE2、Ang(1-7)和Ⅳ型胶原(collagen Ⅳ,ColⅣ)的表达;以酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)法检测血清及肾组织ACE2、Ang(1-7)和肾素含量。[结果]与空白对照组比较,模型组大鼠BUN、Scr水平明显升高,Ccr明显下降(均P<0.01);与模型组比较,消瘀泄浊饮组和贝那普利组大鼠BUN、Scr水平和Ccr明显改善(P<0.01,P<0.05,P<0.05)。与空白对照组比较,模型组肾组织ColⅣ阳性染色面积、总光密度明显升高(均P<0.01),而ACE2、Ang(1-7)阳性染色面积、总光密度均升高(P<0.01,P<0.05);与模型组比较,消瘀泄浊饮组和贝那普利组肾组织ColⅣ阳性染色面积、总光密度下降(均P<0.01),肾组织ACE2、Ang(1-7)阳性染色面积、总光密度明显升高(均P<0.05)。ELISA检测显示,与空白对照组比较,模型组肾组织和血清中肾素含量均显著升高(P<0.01,P<0.01),肾组织中ACE2含量显著升高(P<0.05),Ang(1-7)含量显著下降(P<0.05);血清ACE2、Ang(1-7)含量显著升高(均P<0.01)。与模型组比较,贝那普利组肾组织中肾素含量降低(P<0.05),而消瘀泄浊饮组和贝那普利组血清中肾素含量也降低(均P<0.05);两组肾组织ACE2含量升高(P<0.05),血清ACE2含量下降(P<0.01);而肾组织和血清Ang(1-7)含量均升高(均P<0.05);肾组织炎性细胞浸润及纤维化程度明显降低。消瘀泄浊饮组和贝那普利组数据差异无统计学意义(P>0.05),两组肾组织炎性细胞浸润及纤维化程度也无明显差异。[结论]消瘀泄浊饮通过激活ACE2-Ang(1-7)-MAS轴,减少肾组织ColⅣ的沉积,从而延缓慢性环孢素肾病进展。
英文摘要:
      [Objective]To observe the effect of Xiaoyu Xiezhuo Drink on angiotensin converting enzyme 2-angiotensin(1-7)[ACE2-Ang(1-7)]-MAS axis components in chronic cyclosporine nephropathy(CCN) rats. [Methods]Forty male SD rats were divided into 4 groups: Blank control group, model group, Xiaoyu Xiezhuo Drink group, Benazepril group. The rats model were induced by intragastric administration of 3mg·mL-1 cyclosporine A(CsA) solution accompanied with low salt diet. After 4 weeks, the levels of blood urea nitrogen(BUN), serum creatinine(Scr) were detected by automatic biochemistry analyzer, and creatinine clearance rate(Ccr) was calculated. Pathological changes of renal tissue were observed by hematoxyli-eosine(HE) and Masson staining. The expression of ACE2, Ang(1-7) and collagen Ⅳ(ColⅣ) in renal tissue were detected by immunohistochemistry. The ACE2, Ang(1-7) and renin contents in serum and renal tissue was detected by enzyme-linked immunosorbent assay(ELISA).?摇[Results]Compared with blank control group, the levels of BUN, Scr in model group increased significantly, while Ccr decreased significantly(all P<0.01),compared with model group, the levels of BUN, Scr and Ccr in Xiaoyu Xiezhuo Drink group and Benazepril group were improved significantly(P<0.01, P<0.05, P<0.05). Compared with blank control group, the expression of ColⅣ in renal tissue in model group were significantly up-regulated(P<0.01), while the expression of ACE2, Ang(1-7) in renal tissue were significantly up-regulated(P<0.01, P<0.05); compared with model group, the expression of ColⅣ in renal tissue in Xiaoyu Xiezhuo Drink group and Benazepril group were significantly down-regulated(all P<0.01) and the expression of ACE2, Ang(1-7) in renal tissue were significantly up-regulated(all P<0.05). ELISA showed that compared with blank control group, the content of renin in serum and renal tissue of model group increased(P<0.01, P<0.01),while the content of ACE2 increased in renal tissue(P<0.05), Ang(1-7) decreased(P<0.05); the content of ACE2 and Ang(1-7) in serum increased(all P<0.01). Compared with model group, the content of renin in renal tissue in Benazepril group decreased(P<0.05), and the content of renin in serum in Xiaoyu Xiezhuo Drink group and Benazepril group decreased (all P<0.05); while the content of ACE2 increased in renal tissue(P<0.05) and decreased in serum(P<0.01), but Ang(1-7) was increased both in renal tissue and serum(all P<0.05); and the inflammatory cell infiltration and renal fibrosis decreased obviously. There was no significant difference between Xiaoyu Xiezhuo Drink group and Benazepril group(P>0.05); and there was no significant difference in inflammatory cell infiltration and renal fibrosis between the two groups. [Conclusion]Xiaoyu Xiezhuo Drink can reduce the deposition of colⅣ in renal tissue, thus delays the progression of CCN by activating ACE2-Ang(1-7)-MAS axis.
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