抗纤灵方对阿霉素肾病大鼠肾纤维化作用机制的研究
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摘要
目的观察抗纤灵方对阿霉素肾病模型大鼠肾纤维化的作用机制。方法将SD雄性大鼠随机分为7组,每组8只。其中正常组不做处理,假手术组仅于右侧肾切除,注射0.9%NaCl溶液,余下40只SD大鼠均采取右侧肾切除加尾静脉注射阿霉素制备大鼠阿霉素肾病模型。将造模成功后的大鼠分成模型组,科素亚组,抗纤灵低、中、高剂量组,分别给予相应药物共8周。观察大鼠血清肌酐、尿素氮、24 h尿蛋白定量、α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)表达,HE染色观察肾组织病理。结果抗纤灵方能抑制模型大鼠α-SMA的表达,并减少FN的生成,差异有统计学意义(P<0.05);同时降低24 h蛋白尿,降低血清肌酐、尿素氮,改善肾功能,延缓肾纤维化发展,差异有统计学意义(P<0.05);随着抗纤灵剂量增加,其抗纤维化效应更明显,差异有统计学意义(P<0.05)。结论抗纤灵方能降低24 h尿蛋白定量,改善肾功能,使肾脏病理组织形态学改善,并且呈剂量效应。其机制可能是通过下调α-SMA的表达,抑制FN的生成,从而改善肾纤维化。
Objective To observe the mechanisms of Kangxianling Decoction on renal fibrosis in rats with adriamycin nephropathy. Methods SD male rats were randomly divided into 7 groups,8 rats in each group. The normal group was treated with no surgery,and the sham operation group was treated with 0.9% Na Cl solution after right nephrectomy. The other 40 SD rats were treated with right nephrectomy and intravenous injection of adriamycin to establish the adriamycin nephropathy model. After successful modeling,the model rats were randomly divided into the model group,Cozaar group,Kangxianling Decoction groups with low-,medium-and high-dose. The rats were treated with the corresponding drugs for 8 weeks. The serum creatinine,urea nitrogen,24 h urinary protein excretion,mRNA expressions of α-smooth muscle actin( α-SMA) and fibronectin( FN) in kidney tissue were detected,and the renal pathology was observed after HE staining. Results Compared with the model group,the α-SMA expression and the FN level were significantly decreased in Kangxianling Decoction group,with statistically significant differences( P<0.05). Meanwhile,the levels of 24 h urinary protein excretion,serum creatinine and urea nitrogen were decreased after Kangxianling Decoction treatment,the renal function was improved and the development of renal fibrosis was delayed,with statistically significant differences( P<0.05). The anti-fibrosis effects of Kangxianling Decoction was enhanced with the increase of dosage,with statistically significant differences( P<0.05).Conclusion Kangxianling Decoction can decrease 24 h urinary protein excretion,improve the renal function and pathological histomorphology in a dose-dependent manner. Its mechanism on improving renal fibrosis may be down-regulating the expression of α-SMA and inhibiting the production of FN.
Objective To observe the mechanisms of Kangxianling Decoction on renal fibrosis in rats with adriamycin nephropathy. Methods SD male rats were randomly divided into 7 groups,8 rats in each group. The normal group was treated with no surgery,and the sham operation group was treated with 0.9% Na Cl solution after right nephrectomy. The other 40 SD rats were treated with right nephrectomy and intravenous injection of adriamycin to establish the adriamycin nephropathy model. After successful modeling,the model rats were randomly divided into the model group,Cozaar group,Kangxianling Decoction groups with low-,medium-and high-dose. The rats were treated with the corresponding drugs for 8 weeks. The serum creatinine,urea nitrogen,24 h urinary protein excretion,mRNA expressions of α-smooth muscle actin( α-SMA) and fibronectin( FN) in kidney tissue were detected,and the renal pathology was observed after HE staining. Results Compared with the model group,the α-SMA expression and the FN level were significantly decreased in Kangxianling Decoction group,with statistically significant differences( P<0.05). Meanwhile,the levels of 24 h urinary protein excretion,serum creatinine and urea nitrogen were decreased after Kangxianling Decoction treatment,the renal function was improved and the development of renal fibrosis was delayed,with statistically significant differences( P<0.05). The anti-fibrosis effects of Kangxianling Decoction was enhanced with the increase of dosage,with statistically significant differences( P<0.05).Conclusion Kangxianling Decoction can decrease 24 h urinary protein excretion,improve the renal function and pathological histomorphology in a dose-dependent manner. Its mechanism on improving renal fibrosis may be down-regulating the expression of α-SMA and inhibiting the production of FN.
引文
[1]陈凤,戴恩来.中西医对肾纤维化发病机制的研究进展[J].辽宁中医杂志,2016,43(6):1243-1246.
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[4]何立群,唐英,张昕贤,等.基于抗肾纤维化的益气活血方及有效成分对慢性肾脏病疗效机制分析[J].中国中西医结合肾病杂志,2015,16(4):283-285.
[5]胥晓芳,张权,何立群,等.抗纤灵二号方干预慢性肾脏病肾小管间质损伤的临床研究[J].中国中西医结合肾病杂志,2016,17(2):123-126.
[6]张长明,周家俊,何立群,等.抗纤灵方对CKD3~4期患者疗效及机制的临床多中心随机对照研究[J].辽宁中医杂志,2013,40(1):122-124.
[7]张长明,周家俊,何立群,等.抗纤灵方治疗慢性肾脏病3期患者110例临床研究[J].中医杂志,2013,54(3):214-217.
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[9]陈建,曾莉,陈刚,等.抗纤灵方对Ang II诱导肾纤维化小鼠肾组织α-SMA和I型胶原的影响[J].中华中医药杂志,2017,32(2):739-742.
[10]陈晛,何立群.健脾清化方对肾纤维化大鼠肾功能、蛋白尿及肾组织Col-IV表达的影响[J].南京中医药大学学报,2013,29(6):548-552.
[11]李志辉,易著文.洛沙坦延缓阿霉素肾病鼠慢性病理进展的实验研究[J].中华儿科杂志,2001,39(12):712-717.
[12]徐亚赟,王琛.中药防治慢性肾衰竭肾纤维化作用机制的研究概况[J].中国中西医结合肾病杂志,2017,18(2):177-180.
[13]何伟明,刘不悔,高坤,等.中医药防治肾纤维化的研究现状及实践[J].南京中医药大学学报,2018,34(2):112-117.
[14]李霄,徐静,王斌,等.中药调节细胞外基质治疗肾小球疾病的研究进展[J].中医药信息,2018,35(3):123-126.
[15]钟利平,麻志恒,余柯娜,等.抗纤灵方对5/6肾切除小鼠肾组织纤维化作用机制研究[J].中国实验方剂学杂志,2016,22(2):118-121.
[16]马晓红,何立群.从抑制肾纤维化角度研究健脾清化方对阿霉素肾病大鼠肾功能的作用与机制[J].中国中西医结合杂志,2014,34(6):733-738.
[17]陈刚,张权,张昕贤.何立群教授应用抗纤灵系列方治疗肾脏纤维化经验[J].中国当代医药,2012,19(26):115-116.
[18]麻志恒,钟利平,余柯娜,等.抗纤灵对5/6肾切除诱导的慢性肾纤维化小鼠Akt-mTOR信号通路的影响[J].上海中医药杂志,2015,49(11):67-70.
[19]麻志恒,钟利平,余柯娜,等.抗纤灵对5/6肾切除诱导的慢性肾纤维化小鼠模型不同时期ColI、α-SMA、FN的影响[J].中成药,2017,39(1):181-184.
[2]王金荣,熊洋洋,李斌超,等.肾纤维化的研究进展[J].医学研究杂志,2015,44(6):158-160.
[3]杨兰,陈扬,何小平.近五年中医药关于肾纤维化防治的研究回顾[J].现代中西医结合杂志,2017,26(20):2274-2277.
[4]何立群,唐英,张昕贤,等.基于抗肾纤维化的益气活血方及有效成分对慢性肾脏病疗效机制分析[J].中国中西医结合肾病杂志,2015,16(4):283-285.
[5]胥晓芳,张权,何立群,等.抗纤灵二号方干预慢性肾脏病肾小管间质损伤的临床研究[J].中国中西医结合肾病杂志,2016,17(2):123-126.
[6]张长明,周家俊,何立群,等.抗纤灵方对CKD3~4期患者疗效及机制的临床多中心随机对照研究[J].辽宁中医杂志,2013,40(1):122-124.
[7]张长明,周家俊,何立群,等.抗纤灵方治疗慢性肾脏病3期患者110例临床研究[J].中医杂志,2013,54(3):214-217.
[8]支勇,曹式丽.阿霉素肾病动物模型的国外研究进展[J].中国中西医结合肾病杂志,2008,9(10):933-935.
[9]陈建,曾莉,陈刚,等.抗纤灵方对Ang II诱导肾纤维化小鼠肾组织α-SMA和I型胶原的影响[J].中华中医药杂志,2017,32(2):739-742.
[10]陈晛,何立群.健脾清化方对肾纤维化大鼠肾功能、蛋白尿及肾组织Col-IV表达的影响[J].南京中医药大学学报,2013,29(6):548-552.
[11]李志辉,易著文.洛沙坦延缓阿霉素肾病鼠慢性病理进展的实验研究[J].中华儿科杂志,2001,39(12):712-717.
[12]徐亚赟,王琛.中药防治慢性肾衰竭肾纤维化作用机制的研究概况[J].中国中西医结合肾病杂志,2017,18(2):177-180.
[13]何伟明,刘不悔,高坤,等.中医药防治肾纤维化的研究现状及实践[J].南京中医药大学学报,2018,34(2):112-117.
[14]李霄,徐静,王斌,等.中药调节细胞外基质治疗肾小球疾病的研究进展[J].中医药信息,2018,35(3):123-126.
[15]钟利平,麻志恒,余柯娜,等.抗纤灵方对5/6肾切除小鼠肾组织纤维化作用机制研究[J].中国实验方剂学杂志,2016,22(2):118-121.
[16]马晓红,何立群.从抑制肾纤维化角度研究健脾清化方对阿霉素肾病大鼠肾功能的作用与机制[J].中国中西医结合杂志,2014,34(6):733-738.
[17]陈刚,张权,张昕贤.何立群教授应用抗纤灵系列方治疗肾脏纤维化经验[J].中国当代医药,2012,19(26):115-116.
[18]麻志恒,钟利平,余柯娜,等.抗纤灵对5/6肾切除诱导的慢性肾纤维化小鼠Akt-mTOR信号通路的影响[J].上海中医药杂志,2015,49(11):67-70.
[19]麻志恒,钟利平,余柯娜,等.抗纤灵对5/6肾切除诱导的慢性肾纤维化小鼠模型不同时期ColI、α-SMA、FN的影响[J].中成药,2017,39(1):181-184.