雷公藤多苷对糖尿病肾病大鼠肾小管间质激活素A表达及转分化的影响  

Effects of tripterygium wilfordii polyglucoside on expression of Activin A and influence of transdifferentiation in renal of rats with diabetic nephropathy

作　　者：赵晨光[1] 于为民 任小军 张巍[1] 李慧[1] 

机构地区：[1]山西医科大学,太原030001 [2]山西大医院肾内科

出　　处：《中华医学杂志》2014年第18期1427-1432,共6页National Medical Journal of China

基　　金：山西省卫生厅科技攻关计划项目（2011005）;太原市科技攻关项目（12016907）

摘　　要：目的观察雷公藤多苷（TWP）对糖尿病肾病（DN）大鼠肾小管间质激活素A（Act-A）的表达及转分化的影响。方法将40只Wistar雄性大鼠用随机数字表法分为对照组、DN模型组、厄贝沙坦治疗组、TWP治疗组，每组10只。利用腹腔注射链脲佐菌素（STZ）建立DN大鼠模型，建模后，厄贝沙坦治疗组、TWP治疗组给予相应药物灌胃治疗；第4、8、12、16周末记录大鼠体重、检测24h尿蛋白定量，第16周末处死大鼠，检测血清肌酐（Scr）；取大鼠肾组织行HE、PAS染色，进行病理组织学观察；用免疫组化法检测肾小管间质中Act—A、α平滑肌肌动蛋白（α—SMA）、Ⅳ型胶原（Co—Ⅳ）及E-钙黏蛋白（E—cad）的表达；采用实时荧光定量PCR技术检测肾组织中Act—A、α—SMA、Co—IV及E-cad蛋白mRNA的表达。结果（1）16周后厄贝沙坦治疗组、TWP治疗组的24h尿蛋白[（67．1±9．6）、（61．8±8．0）比（158．3±13．3）mg]、SCr[（31．7±4．1）、（32．6±6．2）比（55．3±8．9）μmol／L]和。肾脏肥大指数[（9．14±0．65）、（7．50±0．34）比（11．28±0．70）mg／g]均低于DN模型组（均P〈0．05），其中厄贝沙坦治疗组和TWP治疗组间比较差异无统计学意义。（2）与DN模型组比较，厄贝沙坦治疗组、TWP治疗组的大鼠体重增加，病理切片均显示肾小管间质病变程度较轻，厄贝沙坦治疗组和TWP治疗组间比较差异无统计学意义。（3）与DN模型组比较，免疫组化和实时荧光定量PCR均显示，厄贝沙坦治疗组、TWP治疗组肾小管间质Act—A、α-SMA、Co—Ⅳ的表达明显低（均P〈0．01），E—cad的表达明显高（P〈0．01），但厄贝沙坦治疗组和TWP治疗组间比较差异无统计学意义。结论TWP能下调Act—A的表达，从而阻碍肾小管间质的转分化，延缓肾脏纤维化。Objective To explore the effects of tripterygium wilfordii polyglucoside （TWP） on expression of Activin A （Act-A） and influence of transdifferentiation in renal tubulointerstitium of rats with diabetes nephropathy （DN）. Methods A total of 40 male Wistar rats were randomly divided into normal control, DN model, irbesartau treatment and TWP treatment groups （ n = 10 each）. The animal model of DN was established by an injection of streptozotocin. After modeling, irbesartan treatment and TWP treatment groups received an intragastric injection of corresponding drugs. The body weights were recorded and the 24 h Pro quantitative levels detected at Weeks 4, 8, 12 and 16 respectively. After sacrificing at Week 16, serum creatinine （Scr） was detected. The renal tissues were excised and examined after HE and PAS staining. The expressions of Act-A, alpha-smooth muscle actin （α-SMA）, collagen type IV （Co-IV） and E-cad in renal tubulointerstitium were detected by immunohistochemistry. And the expressions of Act-A, α-SMA, Co-IV and mRNA of E-cad in renal tissue were detected by real-time quantitative fluorescent polymerase chain reaction （PCR）. Results Compared with DN model group, 24 hPro （ （67.1 ± 9.6）, （ 61.8 ± 8.0 ） vs （ 158.3 ±13.3） mg）, quantitative Scr （ （ 31.7 ±4. 1 ）, （32. 6 ±6. 2） vs （ 55.3 ±8.9 ） μmol/L） and renal hypertrophic index（ （9. 14 ± 0. 65 ）, （7.50 ±0. 34 ） vs （ 11.28 ±0. 70） mg/g） of irbesartan treatment and TWP treatment groups decreased obviously at Week 16 （all P 〈 0. 05 ）. However, no statistical significance existed between irbesartan treatment and TWP treatment groups. The body weights of irbesartan treatment and TWP treatment groups increased versus DN model group. Pathological sections showed that lesion degree of renal tubulointerstitium became alleviated in each group. Yet no statistical significance existed between irbesartan treatment and TWP treatment groups. Both immunohistochemistry and real-time

关 键 词：雷公藤属 糖尿病肾病 激活素A 转分化 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]