双环醇对肾间质纤维化大鼠的干预作用

Intervention effect of bicyclol for rats with renal interstitial fibrosis

目的观察单侧输尿管梗阻(UUO)模型大鼠在双环醇的干预下,肝细胞生长因子(HGF)、转化生长因子-β1(TGF-β1)表达的动态变化,探讨双环醇延缓肾间质纤维化的可能机制。方法将60只雄性SD大鼠随机分为3组:假手术组、模型组、双环醇组,每组各20只,建立单侧输尿管梗阻模型。双环醇组于术前2 d给予双环醇[200 mg/(kg·d)]灌胃,假手术组、模型组给予等量自来水灌胃。每组分别在术后3、6、9、14 d时随机处死5只大鼠并取左侧肾组织,行HE染色观察肾组织病理变化,免疫组织化学染色观察HGF、TGF-β1蛋白的表达,RT-PCR法检测肾组织HGF mRNA的表达水平。结果模型组中HGF蛋白及mRNA表达均呈现早期升高后期降低的趋势,在第6天表达量最高,随后逐渐下降,表达量在术后3、9、14 d与术后6 d比较差异有高度统计学意义(P<0.01)。而TGF-β1蛋白的表达量呈现随梗阻时间延长逐渐升高趋势,术后3、6、9 d与术后14 d比较,差异有高度统计学意义(P<0.01)。在相同时间点,双环醇组与模型组相比,HGF蛋白及mRNA表达量显著升高,差异有高度统计学意义(P<0.01),而TGF-β1蛋白表达量显著降低,差异有统计学意义(P<0.01)。结论双环醇通过上调HGF及下调TGF-β1的表达而发挥缓解肾间质纤维化的作用。

[Abstract] Objective To observe the dynamic change of hepatocyte HGF and TGF-β of UUO rats intervened by bicy- clol, in order to discuss the possible mechanism of renal interstitial fibrosis delayed by bicyclol. Methods 60 male SD rats were randomly divided into sham-operated group （SOR）, UUO model group and bicyclol-treated group （BIC）, each group had 20 rats. Through ligating the left ureter, the unilateral ureteral obstructive rat model was established. 2 days before surgery, the rats in bicyclol-treated group were administed with bicyclol [200 mg/（kg·d）]. Rats in the sham-op- erated group and the model group were administed with tap water. Rats were sacrificed after the surgery for 3, 6, 9 and 14 days. The left kidney was taken. RT-PCR was used to detect the expression of HGF mRNA in renal tissue. The ex- pression of HGF and TGF-β protein were measured by immunohistochemistry. HE stain was used to examine the area of pathological changes. Results In model group, the mRNA and protein expression levels of HGF increased markedly on day 3 and reached its peak value on day 6 after the surgery, then slowly fallen down, and the expression levels on day 6 were significantly different between on day 3, 9, 14 after the surgery, the differences were statistically significant （P 〈 0.01）. However, the protein expression levels of TGF-β increased with extension of obstruction, and the expres- sion levels on day 14 were significantly different from on day 3, 6, 9 after the surgery, the differences were statistically significant （P 〈 0.01）. At each research point, the mRNA and protein expression levels of HGF were significantly high- er in the bicyclol-treated group than those in the model group, the differences were statistically significant （P 〈 0.01）. The protein expression level of TGF-β was significantly lower in the bicyclol-treated group than that in the model group, the difference was statistically significant （P 〈 0.01）. Conclusion Bicyelol can alleviate the degree of renal inter- stitial fibrosis through increasing the expression of HGF and decreasing the expression of TGF-β.