摘要
目的 研究复合乳酸菌肠溶胶囊(LCC)增强肾衰宁胶囊(SSN)对输尿管梗阻(UUO)手术大鼠模型肾纤维化的保护作用.方法 测定LCC中乳酸菌含量,UUO手术建立大鼠肾纤维化模型并每天灌胃给药,21 d后记录终末体重并计算肾系数;生化仪检测BUN、Scr和MAU的变化;病理切片HE染色和Masson染色观察肾脏的组织形态及纤维化程度;免疫组织化学法检测肾组织中α-SMA和Col1A等蛋白表达;ELISA法检测肾组织中IL-6、TNF-α、CRP和TGF-β含量及血清中D-乳酸、内毒素和二胺氧化酶(DAO)含量;Q-PCR法检测回肠组织中ZO-1、Oc-cludin、Claudin-1和Claudin-2的mRNA表达.结果 LCC联合SSN治疗可显著降低UUO肾纤维化大鼠的肾系数,BUN、Scr以及MAU的水平,大鼠体重也显著升高;明显改善肾脏组织形态及胶原蓄积;降低α-SMA和Col1 A蛋白表达,IL-6、TNF-α、CRP、TGF-β、D-乳酸和二胺氧化酶(DAO)含量;升高 ZO-1、Occludin、Claudin-1 的 mRNA表达并降低Claudin-2的mRNA表达,最终起到改善肾纤维化的作用.结论 复合乳酸菌肠溶胶囊(LCC)可增强肾衰宁胶囊(SSN)对肾纤维化的改善作用,其作用主要与抗炎、抗纤维化、调节菌群平衡及改善肠黏膜屏障有关,依据肾-肠轴理论,为治疗肾纤维化提供了依据和新的治疗方法.
Abstract
Objective To investigate the protective effect of Lactic Acid Bacteria Complex Enteric Capsules(LCC)combined with Shenshuaining Capsules(SSN)on renal fibrosis in the ureteral obstruction(UUO)surgical rat models.Meth-ods LCC were tested.The UUO surgery was performed to establish renal fibrosis model in rat models.After drug combina-tion of LCC and SSN for 21 days,terminal body weight was recorded and the renal coefficient was calculated;BUN,Scr and MAU were detected by biochemical instrument;Kidney tissue morphology and the degree of fibrosis were observed and eval-uated by HE and Masson staining;The expression of α-SMA and Col1 A in kidney tissues was determined by immunohisto-chemistry;The content of IL-6,TNF-α,CRP and TGF-β in renal tissue and the content of D-lactate,endotoxin and diam-ine oxidase(DAO)in serum were detected by ELISA;The mRNA expression of ZO-1,Occludin,Claudin-1,and Claudin-2 in the ileal tissue was determined by Q-PCR.Results Compared to SSN group,the rat models with drug combination of LCC combined with SSN treatment significantly reduced renal coefficient,BUN,Scr and MAU;Increased the body weight;Significantly improved renal tissue morphology and collagen accumulation;Decreased the expression of α-SMA and Col 1 A protein,IL-6,TNF-α,CRP,TGF-p,D-lactate and diamine oxidase(DAO);Increased mRNA expression of ZO-1,Occlu-din,Claudin-1 and decreased mRNA expression of Claudin-2,and ultimately improved renal fibrosis.Conclusion LCC can enhance the improvement of SSN on renal fibrosis,and its effect is mainly related to anti-inflammation,anti-fibrosis,regulation of microflora balance and improvement of intestinal mucosal barrier.Based on the renal-intestinal axis theory,it provides a basis and a new treatment method for the treatment of renal fibrosis.
基金项目
江苏省市场监督管理局科技计划项目(KJ21125094)