肾衰宁片对单侧输尿管梗阻大鼠肾间质纤维化的改善作用及机制研究  

Improvement of Shenshuaining tablet on renal interstitial fibrosis in rats with unilateral ureteral obstruction and its mechanism

作　　者：马飞 刘琳[1] MA Fei;LIU Lin(Department of Nephrology,the Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121002,China)

机构地区：[1]锦州医科大学附属第三医院肾脏内科,辽宁锦州121002 [2]赤峰市医院血液净化中心,内蒙古赤峰024099

出　　处：《陕西医学杂志》2022年第6期654-658,共5页Shaanxi Medical Journal

基　　金：内蒙古自治区自然科学基金资助项目(2021MS08061)。

摘　　要：目的:探讨肾衰宁片对单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的改善作用,并分析其可能机制。方法:选取Wistar雄性大鼠45只,随机分为假手术组(S组)、模型组(U组)和治疗组(T组),每组15只。造模成功后,T组从术后的第1日起每日用肾衰宁片0.19 g/(kg·d)灌胃,U组和S组每日给同体积的0.9%氯化钠溶液灌胃。三组大鼠在术后7、14、21 d分别处死5只。检测血清肌酐(CREA)、尿素氮(BUN)和尿微量白蛋白(mAlb)并进行比较。采用HE染色法观察三组大鼠RIF病变严重程度并进行评分比较。采用Masson染色法观察三组大鼠肾间质胶原体积分数(CVF)变化情况。采用免疫组化染色检测肾间质中Wnt和β-catenin的平均光密度(AOD)并进行比较。结果:术后7、14、21 d,U组血清CREA、BUN水平显著高于S组和T组,且T组高于S组(均P<0.05)。术后7、14 d,三组大鼠尿mAlb水平比较差异无统计学意义(均P>0.05)。术后21 d三组大鼠尿mAlb水平出现显著变化,S组尿mAlb水平最低,T组次之,U组最高,三组比较差异有统计学意义(均P<0.05)。术后7、14、21 d,U组及T组大鼠RIF病变严重程度评分明显高于S组(均P<0.01);与U组比较,T组各时间点RIF病变严重程度评分降低,但仍高于S组(均P<0.05)。术后7、14、21 d,U组和T组肾间质CVF高于S组,且随梗阻时间推移CVF呈进行性增高(均P<0.05);T组术后各时间点CVF高于S组,但低于U组(均P<0.05)。采用Image J软件计算Wnt1和β-catenin AOD后进行比较,S组最低,且术后各时间点AOD比较差异无统计学意义(均P>0.05);U组和T组AOD高于S组,且随梗阻时间推移AOD呈进行性增高(均P<0.05);T组术后各时间点AOD高于S组,但低于U组(均P<0.05)。结论:肾衰宁片可改善UUO大鼠RIF程度,保护肾功能,降低尿mAlb水平,其机制可能与抑制Wnt/β-catenin信号通路有关,选择性抑制Wnt/β-catenin信号通路可能为纤维化肾病的治疗提供新的策略。Objective:To investigate the improvement of Shenshuaining tablet on renal interstitial fibrosis(RIF)in rats with unilateral ureteral obstruction(UUO)and analyze its possible mechanism.Methods:Forty-five male Wistar rats were randomly divided into sham group(group S),model group(group U)and treatment group(group T),with 15 rats in each group.After successful modeling,group T was gavaged with 0.19 g/(kg·d)of Shenshuaining tablets daily from the 1st postoperative day,and group U and group S were gavaged with the same volume of 0.9%sodium chloride solution daily.Five rats in the three groups were killed at 7,14 and 21 days after operation.Serum creatinine(CREA),blood urea nitrogen(BUN)and urine microalbumin(mAlb)were measured and compared.The severity of RIF lesions in the three groups was observed by HE staining and the scores were compared.Masson staining was used to observe the changes of collagen volume fraction(CVF)in the three groups.The mean optical densities(AOD)of Wnt andβ-catenin in renal interstitium were detected and compared by immunohistochemical staining.Results:At 7,14 and 21 days after operation,serum CREA and BUN levels in group U were significantly higher than those in group S and group T,and those in group T were higher than those in group S(all P<0.05).At 7 and 14 days after operation,there was no significant difference in urine mAlb level among the three groups(all P>0.05).Urine mAlb levels of three groups showed significant changes at 21 days after operation.The urine mAlb level in group S were the lowest,followed by group T,and the highest in group U,and the differences among the three groups were statistically significant(all P<0.05).At 7,14 and 21 days after operation,the RIF severity score in group U and group T was significantly higher than that in group S(all P<0.01);compared with U group,the RIF severity score in group T was lower at all time points,but still higher than that in group S(all P<0.05).At 7,14 and 21 days after operation,renal interstitial CVF in group U and groupT was hig

关 键 词：单侧输尿管梗阻 肾衰宁片 肾功能 肾间质纤维化 WNT/Β-CATENIN信号通路 大鼠 

分 类 号：R692[医药卫生—泌尿科学]