苦参碱抗大鼠胰腺纤维化作用及机制研究  

A mechanism study of sophorcarpidine in treatment of pancreatic fibrosis.

作　　者：任洪波[1] 孙自勤[1] 李延青[2] 阎明先[2] 孟敏[2] 寇毅[2] 王志宇[2] 

机构地区：[1]济南军区总医院消化科,山东250031 [2]山东大学齐鲁医院消化科

出　　处：《胰腺病学》2007年第2期90-93,共4页Chinese JOurnal of Pancreatology

基　　金：山东省中医药发展基金资助（20051034）

摘　　要：目的探讨苦参碱对胰腺纤维化的干预作用，为其临床应用提供实验依据。方法48只雄性Wistar大鼠随机分为正常组、模型组和治疗组，每组16只。以腹腔注射DDC（750mg／kg体重）每周2次，共6周建立胰腺纤维化动物模型，治疗组于DDC注射后2周起每日腹腔注射苦参碱（100mg／kg体重），6周后处死动物。采用放射免疫法检测血清透明质酸。胰腺常规病理检查、评分，Masson染色判断胶原纤维量。免疫组化和RT—PCR法检测胰腺组织生长因子131（TGF-β1）及Smad3、Smad7的蛋白和mRNA表达。结果治疗组血清透明质酸浓度、病理积分及胶原纤维的表达量分别为（105．85±25．69）ng／ml、3．16±1．15及（19．16±4．27）％，TGF-β1和Smad3蛋白表达分别为（23．16±7．68）％和（18．65±9．82）％，TGF-β1mRNA和Smad3mRNA表达分别为0．33±0．10和0．23±0．03，均较模型组明显降低（P〈0．01）。而Smad7的表达与模型组无显著差异。结论大鼠腹腔注射DDC可建立胰腺纤维化动物模型。苦参碱具有显著的抗胰腺纤维化的作用，其机制可能与抑制TGF-β1的产生、抑制TGF-β／Smads信号转导通路活性有关。Objective To investigate the effect and mechanism of sophorcarpidine in the treatment of pancreatic fibrosis in an attempt to provide reference for clinical application of sophorcarpidine. Methods Forty-eight male Wistar rats were equally randomized into three groups： the normal group, the model group and the sophorcarpidine treatment group. Pancreatic fibrosis was induced by intraperitoneal injection with diethyldithiocarbamate （DDC 750 mg/kg body weight） in rats. Serum hyaluronic acid was detected by radioimmunology. Pancreatic fibrosis was scored by HE stain and the amount of collagenous fibers was measured by Masson stain. The protein and mRNA expressions of TGF-β1, Smad3 and Smad7 in the pancreas were examined by immunohistochemistry and RT-PCR. Results Serum hyaluronic acid level in the treatment group was significant lower than that in the control group [,（105.85 ± 25.69）ng/ml vs （197.36 ± 22. 46）ng/ml, P 〈 0. 01）]. The score of pancreatic fibrosis in the treatment group was significant lower than that in the model group by HE stain（3.16 ± 1.15） vs 6.87 ± 2.24）, and the amount of collagenous fibers in the treatment group was also significantly lower than that in the model group[（19. 16 ±4. 27）% vs （47. 57 ± 6. 15）%, P 〈 0.01 ）]. Protein expression levels of TGF-β1, Smad3 and Smad7 detected by IH in the model group were significantly higher than those in the normal group. TGF-β1 and Smad3 levels in the treatment group were significantly lower than those in the model group, but there was no significant difference in Smad7 level between the model groups and treatment group. Changes in expression of TGF-β1 mRNA, Smad3 mRNA and Smad7 mRNA detected by RT-PCR were similar to the results of these protein expressions. Conclusions Sophorcarpidine had a notable anti-fibrosis effect on pancreatic fibrosis induced by intraperitoneal injection with DDC. The anti-fibrosis mechanism is possibly related to its inhibitory effect on the production of TGF-β1 and the activity of T

关 键 词：苦参碱 胰腺 纤维化 转化生长因子Β 

分 类 号：R28[医药卫生—中药学]