甘草酸18α体调节梗阻性肾病大鼠肾间质中CTGF和TGF-β1表达的实验研究

Effects of glycyrrhizin-18α on expressions of CTGF and TGF-β1 in renal interstitium in rats with obstructive nephropathy

目的 探讨甘草酸 18α体对梗阻性肾病大鼠肾间质中CTGF和TGF β1蛋白表达的影响。 方法 10 0只Wistar大鼠数字表法随机分成实验组 (甘草酸预防组、甘草酸治疗组、生理盐水组 )和对照组 (假手术组 )。实验组大鼠结扎单侧输尿管建立梗阻性肾病模型。分别于术后 7、14、2 8和 5 6d处死实验动物 ,切取肾皮质部位组织 ,用光镜、电镜观察肾间质的病理形态学变化 ;用免疫组织化学染色检测肾间质中CTGF、TGF β1蛋白和Ⅲ型胶原蛋白的表达 ,并用EIG综合图象分析系统对其表达进行半定量分析。结果 模型显示肾间质呈进行性纤维化。半定量分析发现 ,手术后 7d ,甘草酸治疗组和预防组与假手术组相比较 ,肾间质中CTGF、TGF β1和Ⅲ型胶原蛋白表达呈进行性显著增多 (P <0 0 1) ,与生理盐水组相比较呈进行性显著减少 (P <0 0 1) ,但甘草酸治疗组和预防组之间无明显差异 (P >0 0 5 )。相关分析发现 ,肾间质中CTGF的表达量与TGF β1和Ⅲ型胶原的表达呈显著性正相关 (r =0 63和 0 6g ,P <0 0 1)。 结论 甘草酸可能通过下调梗阻性肾病大鼠肾间质CTGF和TGF β1的表达 ,抑制肾间质纤维化的发生。

Objective To investigate the effects of glycyrrhizin-18α on the expressions of connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1) in renal interstitium in rats with obstructive nephropathy. Methods A total of 100 Wistar rats were divided into experiment group (include prophylaxis group with glycyrrhizin-18α, glycyrrhizin-18α treatment group, and group with normal saline) and control group (sham operation group). Models of rats with obstructive nephropathy were established by unilateral ureteral ligation. The rats were sacrificed at 7, 14, 28, and 56 d after operation and specimens were taken from the renal cortex. The morphopathological changes in the renal interstitium were observed byr light and electron microscopy. CTGF, TGF-β1, and collagen type Ⅲ were detected by immunohistochemical staining. The measured data were evaluated by EIG image analysis system. Results In the renal interstitium, there was progressive fibrosis in the model. Semi-quantitative analysis indicated that the expression levels of CTGF, TGF-β1, and collagen type Ⅲ in the renal interstitium in glycyrrhizin-18α treatment and prophylaxis groups were markedly higher than those in the sham operation group (P<0.01), but were significantly lower than those in the normal saline group (P<0.01) at 7 d after operation. There was no significant difference between the treatment group and the prophylaxis group (P>0.05). The expression of CTGF in the renal interstitium was closely correlated with those of TGF-β1 and collagen type Ⅲ (P<0.01). Conclusion Glycyrrhizin-18 α may inhibit renal interstitial fibrosis in rats with obstructive nephropathy by down-regulating the expressions of CTGF and TGF-β1 in the rat renal interstitium.