养阴活血方药对环孢素A慢性肾毒性的影响  

Experimental Research of Nourishing Yin and Promoting Blood Circulation Formula on Chronic Nephrotoxicity of Cyclosporine A in Rats

作　　者：刘洲[1] 周胜 姚晓峰[1] 孝晨[1] 缪新文[1] 毕革文[1] 张靖[1] 

机构地区：[1]广州中医药大学祈福医院肾脏中心,广州511495 [2]广东省佛山市南海金沙医院,佛山528223

出　　处：《中国中西医结合肾病杂志》2005年第8期449-452,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：广东省中医药管理局科研基金资助项目(No.100054)

摘　　要：目的:探讨养阴活血方药对环孢素A(CsA)慢性肾毒性的治疗作用。方法:将40只SD大鼠随机分为高剂量组、低剂量组、对照组、空白组,采用钠耗竭法建立CsA慢性肾毒性大鼠模型,分别以20倍成人剂量养阴活血方药、5倍成人剂量养阴活血方药、10倍成人剂量依那普利及自来水灌胃4周,分别于第1、2、3、4周末检测24h尿蛋白定量、血肌酐、肌酐清除率;光镜观察大鼠肾脏病理,免疫组化法测定TGF-β1、FN、Ⅳ型胶原,采用RT-PCR技术测定中药对肾间质TGF-βmRNA表达的影响并对各组结果进行比较。结果:空白组24h尿蛋白定量4周后稍有上升,但无统计学差异(P>0.05)。对照组治疗后24h尿蛋白定量呈显著性下降(P<0.05)。低剂量组治疗后24h尿蛋白定量亦呈下降趋势(P<0.05)。高剂量组治疗4周后24h尿蛋白定量降低较低剂量组明显,但无统计学差异(P>0.05);空白组治疗后血肌酐值呈上升趋势但无统计学差异(P>0.05);对照组及高、低剂量组治疗后第4周血肌酐值较第1周有明显下降,均有统计学差异(P<0.05)。对照组及高、低剂量组与空白组治疗后有统计学差异(P<0.01)。空白组治疗后肌酐清除率无明显变化(P>0.05),对照组及高、低剂量组治疗后肌酐清除率呈上升趋势,无统计学差异(P>0.05)。各组经治疗4周后大鼠肾皮、髓质交界区可见肾小管上皮细胞空泡变性,部分小管上皮细胞萎缩及轻度的间质纤维化,淋巴或单核细胞浸润。空白组明显,对照组及中药高、低剂量组改变有不同程度减轻,以高剂量组肾间质空泡变性改善明显。各实验组肾间质均表达TGF-β1、FN、Ⅳ型胶原,其中空白组上述成分的表达遍布皮髓质肾小管,灌喂依那普利及中药后表达程度减轻,而以中药高剂量组减轻更为明显。各组肾间质均表达不同程度的TGF-β1mRNA,其表达的丰富程度按空白组、对照组、低剂量组和高剂量组依次减弱。结论:Objective：To study the effect of traditional chinese medicine nourishing yin and promoting blood circulation formula on chronic nephrotoxicity of cyclosporine A（CsA） in rats. Methods： 40 SD rats were divided into the highdosage group, low - dosage group, control group and blank group randomly. The model were set up by Salt depletion . The high dosage group were gastric.ally injected with 20 times dosage of the subject medicine that the people take while the low dosage group 5 times. The control group was gastric.ally injected with 10 times dosage Enalapril. The blank group was treated by gastric infusion of water. The blood specimen and 24 hours urine were collected at the weekend of 1st, 2nd,3rd and 4th .Blood creatinine and endogenous creatinine clearance rate as well as the 24 hours urinary protein were examined respectively.Renal pathological changes were observed by light microscope. Influence of Chinese herbal medicine on expression of TGF-β1, FN and Ⅳ collagen was examined by Imrnunohistochemistry . Influence of the drugs on expression of interstitial TGF-β1 mRNAwas detected by RT- PCR method. Results：The quantity of 24 hours urinary protein rose little in the blank group during the experiment。 No significantly difference was found（ P 〉 0.05）. The quantity of 24 hours urine protein descended significantly in the control groupand treated groups（P〈0.05）. Serum creatinine rose insignificantly in the blank group （P〉0.05 ） while significantly descended （ P 〈 0.05） in the control group, and treated groups. There was very significant difference between the high dosage, the low dosage, the control group and the blank group（P〈0.01）. Creatinine clearance had no change in the blank group during the experiment （P 〉 0.05）. In the control group and treated group, creatinine clearance tented to increase, however, the difference was no significant （P〉0.05） b after treatment. A great deal of sheet loose Vacuolar changes of renal tubules epithelia in combination of c

关 键 词：养阴活血 间质纤维化 环孢素A 肾毒性 中医药疗法 实验研究 养阴活血方 慢性肾毒性 中药对 24H尿蛋白定量 

分 类 号：R285[医药卫生—中药学]