生、熟地黄缓解肾间质纤维化的作用及其机制研究

Rehmanniae Radix and Rehmanniae Radix Praeparata Ameliorates Renal Interstitial Fibrosis Induced by Unilateral Ureteral Occlusion in Rats and Their Mechanism

目的:探讨生地黄和熟地黄对单侧输尿管梗阻模型(UUO)大鼠肾间质纤维化的作用及其机制。方法:雄性SD大鼠随机分为生地黄水煎液组、熟地黄水煎液组、模型对照组、假手术组,每组5只。生地黄水煎液组、熟地黄水煎液组分别按生地黄、熟地黄剂量1.6 g/(kg·d)灌胃给药14 d,测定血清肌酐(Scr)、尿素氮(BUN)。HE染色、Masson染色观察肾脏组织病理学变化,免疫印迹检测TGF-β1、α-SMA和Collagen-Ⅰ的表达。结果:与模型组比较,各给药组大鼠Scr、BUN值显著降低(P<0.05);肾小球玻璃样病变减轻,肾小管囊性扩张和空泡变性程度缓解,胶原沉积减少,肾间质纤维化程度明显改善;TGF-β1、α-SMA和Collagen-Ⅰ表达显著降低(P<0.05)。与熟地黄水煎液组比较,生地黄水煎液组的Scr、BUN值较低,胶原沉积较少,肾间质纤维化改善较明显,α-SMA表达显著减少(P<0.05)。结论:生地黄和熟地黄均能缓解肾间质纤维化,以生地黄作用较强,其作用机制可能与下调TGF-β1、α-SMA和Collagen-Ⅰ的表达有关。

Objective： To study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on renal interstitial fibrosis（ RIF） of obstructed kidneys in a unilateral ureteral obstruction（ UUO） rat model and the mechanism. Methods： 20 rats were randomly divided into four groups： sham operated group,UUO group,Rehmanniae Radix decoction group and Rehmanniae Radix Praeparata decoction group. The sham operated group and the UUO group were orally administered normal saline,the drug groups were orally administered 1. 6 g /（ kg·d） of Rehmanniae Radix decoction and Rehmanniae Radix Praeparata decoction for 14 days,respectively. Then the serum of rats were collected for measurements of Scr and BUN contents. Histological changes of kidneys were observed by HE and Masson staining. The expression of transforming growth factor-β1（ TGF-β1）,α-smooth muscle actin（ α-SMA） and type Ⅰ collagen（ Collagen-Ⅰ） were detected by Western blot method. Results： Compared with model group,the contents of Scr and BUN in rats serum of drug groups were significantly decreased（ P〈0. 05）,the sclerosis of glomerulus was ameliorated,the degree of saccular dilatation and the damage of tubules were alleviated,collagen distribution and interstitial fibrosis was obviously improved,while the expressions of TGF-β1,α-SMA and Collagen-Ⅰwere decreased. Compared with Rehmanniae Radix Praeparata decoction group,the contents of Scr and BUN in rats serum of Rehmanniae Radix decoction group were lower,the decrease of collagen distribution and interstitial fibrosis were more obviously,while the expression of α-SMA was significantly decreased（ P〈0. 05）. Conclusion： The effect of Rehmanniae Radix is more powerful than that of Rehmanniae Radix Praeparata on attenuating interstitial fibrosis,which may relative to downregulating the expressions of TGF-β1,α-SMA and Collagen-Ⅰ.