百令胶囊对肾小管间质纤维化大鼠肾脏α-平滑肌肌动蛋白表达的影响及意义

The effects of bailing capsules on the expression of α-SMA in the rats with tubulointerstitial fibrosis

目的观察百令胶囊对肾小管间质纤维化大鼠肾脏α-平滑肌肌动蛋白(α-smooth muscleactin,α-SMA)表达的影响,探讨百令胶囊肾脏保护作用的可能机制。方法雄性3个月龄SD大鼠90只,随机分为:对照组(30只),模型组(30只),预防组(30只),以腺嘌呤灌胃法建立大鼠肾小管间质纤维化模型,预防组加以1.5 g/(kg.d)百令胶囊溶于生理盐水灌胃以预防肾小管间质纤维化;对照组以等体积的2%淀粉溶液和生理盐水灌胃。分别于实验第7、12、17周时随机处死10只大鼠,进行血肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen BUN),24 h尿蛋白定量和尿N乙-酰-β-D氨-基葡萄糖苷(N-a-cetylβ--D-glucosam inidase,NAG)酶检测,光镜下观察肾组织的病理变化及免疫组织化学法检测肾脏转化生长因子-β1(transform ing growth factor-beta1,TGFβ-1)、α-SMA的表达情况。结果①功能学变化:与对照组比较,各时相点模型组、预防组大鼠尿蛋白、尿NAG酶、血Cr及血BUN均升高(P<0.01),但预防组低于模型组(P<0.01);模型组、预防组自身对照各指标均较前一时相点升高(P<0.01)。②病理学变化:7周时模型组、预防组即有肾小管间质损害;模型组、预防组自身对照肾小管间质损害均较前一时相点加重(P<0.01),但7、12周时预防组肾小管间质损害均较模型组为轻(P<0.01),17周时两组间差异无统计学意义(P=0.670)。③免疫组化:各时相点模型组、预防组大鼠肾脏TGFβ-1、α-SMA的表达均高于对照组(P<0.01),但预防组均低于模型组(P<0.01),模型组、预防组自身对照均较前一时相点升高(P<0.01),17周时表达量最高。结论百令胶囊可能通过抑制α-SMA,在肾小管间质纤维化早期应用时起到保护作用。

Objective To observe the effects of bailing capsules on the expression of α-SMA in the rats with tubulointerstitial fibrosis to explore the possible mechanism of renal-protecting of bailing capsules. Methods 90 male Sprague-Dawley（SD） rats, aged three months, were randomly divided into three groups：control group （n = 30） ,model group（ n = 30） ,treatment group（ n = 30）. The renal tubulointerstitial fibrosis model was established by gavage with 150 mg/（ kg.d）adenine solved by a solution of 2 percent starch and bailing capsules solved by normal saline was gave to the rats from treatment group in a dose of 1.5 g/（ kg.d） and the same volume starch and normal saline were gave to the rats from control group. At week 7,12,17, ten rats of every group were killed, the urinary protein, N-acetyl-β-D-glucosaminidase （NAG） in the urine and renal profile including BUN and serum creatinine were examined. The histological changes of kidney were observed by light microsco- py, and the expression of TGF-β1, α-SMA were examined by immunohistochemistry staining. Results At 7,12, 17 weeks, the value of urinary protein, urinary NAG, serum BUN and serum Cr of rats from model and treatment group were higher than those of control one （ P 〈 0.01 ）, but those of treatment group was lower than those of model group （ P 〈 0. 01 ）. The value of urinary protein, urinary NAG, serum BUN and serum Cr of rats from model and treatment group were increase, the highest in the 17th week. Renal interstitium injury was seen in model group and treatment group rats at week 7, and became aggravating after 7 weeks. The degree of renal interstitium fibrosis in rats from treatment group was lighter than that of model group at week 7 and 12 （P 〈 0. 01 ）, but there was not a significantly difference at week 17 （P = 0. 670） ; the expression of TGF-β1, α-SMA in rats from model and treatment group were higher than those of control group （ P 〈0. 01 ）, and treatment group was lower than model group（P 〈 0. 01 ）. The expression of TGF-β1, α-SMA in rats from model and treatment group were increase, and the highest in the 17th week. Conclusion These results suggest that bailing capsules suppressed fibrogenic events accompanied by a decreased in α-SMA expression at the early stage of TIF.