SB203580对肝纤维化大鼠肝脏Ⅰ、Ⅲ型胶原蛋白表达的影响  

SB203580 decreases collagen Ⅰ and collagen Ⅲ expression in the liver of rats with experimental hepatic fibrosis

作　　者：杨新疆[1] 齐翠花[2] 郑勇[2] 曹玉文[3] 李睿[2] 宋丽秀[2] 赵强[1] 陈卫刚[2] 

机构地区：[1]石河子大学医学院,新疆维吾尔自治区石河子市832002 [2]石河子大学医学院第一附属医院消化内科,新疆维吾尔自治区石河子市832008 [3]石河子大学医学院第一附属医院病理科,新疆维吾尔自治区石河子市832008

出　　处：《世界华人消化杂志》2014年第3期310-318,共9页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81170402~~

摘　　要：目的:探讨SB203580对肝纤维化大鼠肝脏Ⅰ、Ⅲ型胶原蛋白表达的影响.方法:将32只♀SD大鼠分为4组:正常组(N组)8只、肝纤维化组(HF组)8只、DMSO溶剂干预组(D组)8只、P38MAPK抑制剂SB203580干预组(SB组)8只.采用四氯化碳复合因素法复制肝纤维化模型,肝纤维化模型制作结束后,D组给予2‰DMSO溶液3 mL/(kg?d),SB组给予SB203580溶液10 mg/(kg?d),N组、HF组给予同等剂量0.9%生理盐水3 mL/(kg?d)腹腔注射,连续注射4 d.干预结束后,宰杀大鼠留取肝脏,行肝组织病理切片HE染色评价肝纤维化分期,行Masson染色观察胶原纤维沉积情况,采用SP免疫组织化学法检测肝脏Ⅰ、Ⅲ型胶原蛋白表达,应用逆转录PCR法检测肝脏中Ⅰ、Ⅲ型胶原mRNA表达.结果:正常对照组(N组)、肝纤维化组(H F组)、S B203580溶剂组(D M S O组)和P38MAPK通路特异性抑制剂组(SB203580组)的肝纤维化分期平均秩分别为4.50、22.50、24.00和15.00;SSS评分分别为2.750±0.707、15.875±0.835、16.000±0.926和11.625±0.9 1 6;Ⅰ型胶原显色指数分别为1.5 7 5±0.249、7.650±0.621、7.725±0.501和4.625±0.495;Ⅲ型胶原显色指数分别为2.375±0.518、4.025±0.446、4.075±0.544和3.375±0.167;Ⅰ型胶原mRNA表达分别为0.020±0.003、0.012±0.002、0.009±0.002和0.016±0.005;Ⅲ型胶原mRNA表达分别为0.412±0.772、0.773±0.137、0.799±0.116和0.572±0.862.HF组与N组相比,Ⅰ、Ⅲ型胶原及其mRNA表达升高(均P<0.001),与肝纤维化分期结果一致(P<0.001);D组与HF组无明显差异(均P>0.05);SB组与HF组相比,Ⅰ、Ⅲ型胶原表达降低(Ⅰ型胶原显色指数P<0.001,Ⅲ型胶原显色指数P=0.041);Ⅰ型胶原mRNA表达降低(P=0.005),同时Ⅲ型胶原mRNA表达亦降低(P=0.005),肝纤维化分期下降(P=0.015).结论:P38MAPK抑制剂SB203580阻断P38MAPK通路具有降低肝脏Ⅰ、Ⅲ型胶原表达的作用,能够延缓肝纤维化的发生发展.AIM： To investigate the effect of P38MAPK in- hibitor SB203580 on collagen I and collagen III expression in the liver of rats with experimental hepatic fibrosis. METHODS： Thirty-two female SD rats were ran- domly divided into four groups： a normal control group, a hepatic fibrosis group, a dimethyl sulfoxide （DMSO） group and a SB203580 group. Except the normal control group, rats in other groups were subcutaneously injected with car- bon tetrachloride to induce hepatic fibrosis. The DMSO group was intraperitoneally injected with 2%o DMSO [3 mL/（kg·d）]. Rats in the SB203580 group were intraperitoneally injected with SB203580 [10 mg/（kg·d）, dissolved in DMSO]. Fibrosis was staged using histopathological methods. The expression of collagen I and col- lagen III was detected by immun0histochemistry and RT-PCR. RESULTS： In the normal control group, hepatic fibrosis group, DMSO group and SB203580 group, mean rank of liver fibrosis stage was 4.50, 22.50, 24.00 and 15.00, respectively; SSS scores were 2.750±0.707, 15.875 ±0.835, 16.000 ±0.926 and 11.625 ± 0.916, respectively; color rendering indexes of col- lagen I were 1.575± 0.249, 7.650± 0.621, 7.725 ± 0.501 and 4.625 ± 0.495, respectively; color render- ing indexes of collagen III were 2.375 ± 0.518, 4.025 ± 0.446, 4.075 ± 0.544 and 3.375± 0.167, respec- tively; the relative expression levels of collagen I were 0.020 ± 0.003, 0.012 ± 0.002, 0.009 ± 0.002 and 0.016 ± 0.005, respectively; the relative expression levels of collagen III were 0.412± 0.772, 0.773± 0.137, 0.799 ± 0.116 and 0.572± 0.862, respectively. Compared to the normal control group, the stage of fibrosis was elevated （P 〈 0.001） and the expres- sion of collagen I and collagen III was increased （both P 〈 0.001） in the hepatic fibrosis group. Com- pared to the hepatic fibrosis group, the stage of fibrosis declined （P = 0.015） and the expression of collagen I （P 〈 0.001） and collagen III （P = 0.041） was decreased in the SB203580 group. CON

关 键 词：SB203580 肝纤维化 Ⅰ型胶原 Ⅲ型胶原 

分 类 号：R575.2[医药卫生—消化系统]