CAJ | 학술논문

目的通过观察来氟米特对局灶节段性肾小球硬化(FSGS)大鼠肾组织转化生长因子(TGF)-β1表达水平变化的影响,探讨来氟米特对肾脏保护作用的可能机制.方法将24只SD大鼠按体质量简单随机分3组:正常对照组、FSGS模型组、来氟米特治疗组,每组各8只大鼠.采用单侧肾切除1周后重复注射多柔比星法建立FSGS模型.术后2周起,来氟米特治疗组给予来氟米特混悬液5 mg/(kg·d)灌胃,正常对照组、FSGS模型组给予等量溶媒灌胃.于实验第8周末将各组大鼠处死并收集标本,记录血肌酐、尿素氮、总胆固醇、清蛋白及24 h尿蛋白排泄量;取肾组织行病理检查并计算肾小球硬化指数(GSI);免疫组织化学法检测TGF-β1在肾脏的表达;Western blot检测TGF-β1在肾组织的蛋白表达.结果与正常对照组比较,FSGS模型组及来氟米特治疗组大鼠24 h尿蛋白排泄量、血肌酐、尿素氮、胆固醇均显著升高,而血清清蛋白则明显降低,肾组织病理改变较重且TGF-β1蛋白表达明显升高,差异均有统计学意义(P均＜0.05);与FSGS模型组比较,于实验第8周末,来氟米特治疗组大鼠24 h尿蛋白排泄量、相关血清生化指标及肾组织病理改变均有不同程度改善,且肾组织TGF-β1蛋白表达下降,差异均有统计学意义(P均＜0.05).结论来氟米特可通过抑制TGF-β1的表达,减轻FSGS肾组织纤维化程度,从而保护肾脏.
목적 통과관찰래불미특대국조절단성신소구경화(FSGS)대서신조직전화생장인자(TGF)-β1표체수평변화적영향,탐토래불미특대신장보호작용적가능궤제.방법 장24지SD대서안체질량간단수궤분3조:정상대조조、FSGS모형조、래불미특치료조,매조각8지대서.채용단측신절제1주후중복주사다유비성법건립FSGS모형.술후2주기,래불미특치료조급여래불미특혼현액5 mg/(kg·d)관위,정상대조조、FSGS모형조급여등량용매관위.우실험제8주말장각조대서처사병수집표본,기록혈기항、뇨소담、총담고순、청단백급24 h뇨단백배설량;취신조직행병리검사병계산신소구경화지수(GSI);면역조직화학법검측TGF-β1재신장적표체;Western blot검측TGF-β1재신조직적단백표체.결과 여정상대조조비교,FSGS모형조급래불미특치료조대서24 h뇨단백배설량、혈기항、뇨소담、담고순균현저승고,이혈청청단백칙명현강저,신조직병리개변교중차TGF-β1단백표체명현승고,차이균유통계학의의(P균＜0.05);여FSGS모형조비교,우실험제8주말,래불미특치료조대서24 h뇨단백배설량、상관혈청생화지표급신조직병리개변균유불동정도개선,차신조직TGF-β1단백표체하강,차이균유통계학의의(P균＜0.05).결론 래불미특가통과억제TGF-β1적표체,감경FSGS신조직섬유화정도,종이보호신장.
Objective To explore the possible mechanisms of the protective effect of leflunomide on kidneys by observing the effects of leflunomide on rat kidney tissue of focal segmental glomerulosclerosis (FSGS) expression level of transforming growth factor (TGF)-β1.Methods Twenty-four SD rats were randomly divided into 3 groups:normal control group (n =8),FSGS model group (n =8) and leflunomide treatment group (n =8).Unilateral nephrectomy 1 week after repeated injection of doxorubicin established FSGS model.Since 2 weeks after surgery,the treatment group had been given the leflunomide suspension 5 mg/(kg · d) orally,while normal control group and model group had been given the same amount of solvent orally.In the 8th week of the experiment,the rats were sacrificed and the specimens were collected,so serum creatinine,blood urea nitrogen,total cholesterol,albumin and 24 hours urinary protein were recorded; renal tissue was taken for pathological examination and calculation of glomerular sclerosis index (GSI) was made;immunohistochemical detection of TGF-β1 expression in the kidney was performed;The expression of TGF-β1 was examined by Western blot.Results Compared with normal control group,FSGS model group and leflunomide treatment group rats' 24 hours urinary protein excretion,serum creatinine,blood urea nitrogen,and cholesterol significantly increased while serum albumin significantly reduced severe renal pathological changes and TGF-β1 protein expression was significantly increased,and the differences were statistically significant (all P ＜ 0.05) ; Compared with the FSGS model group,in the 8th weekend of the experiments,the treated rats' 24 hours urinary protein excretion,relevant serum biochemical indicators of renal pathological changes had different degrees of improvement in renal tissue and TGF-β1 protein expression was decreased,so the differences above were statistically significant(all P ＜ 0.05).Conclusions Leflunomide may reduce the FSGS kidney tissue fibrosis by inhibiting the expression of TGF-β1,and thus protect the kidneys.