棉酚对糖尿病大鼠非酒精性脂肪性肝病纤维化的影响  

Effect of gossypol on hepatic fibrosis of nonalcoholic fatty liver disease in diabetic rats

作　　者：李秧秧[1] 陈涵斌[2] 徐菲菲 万丽[1] 陈国荣[1] 陈垒 陈三妹[4] 王蓉蓉[1] LI Yangyang;CHEN Hanbin;XU Feife;WAN Li;CHEN Guorong;CHEN Lei;CHEN Sanmei;WANG Rongrong(Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015;De- partment of Radiation and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015;The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325035;Department of Nursing, School of Medical Sciences, Shaoxin~, University. Shaoxine. 312000)

机构地区：[1]温州医科大学附属第一医院病理科,浙江温州325015 [2]温州医科大学附属第一医院放化疗科,浙江温州325015 [3]温州医科大学第一临床医学院,浙江温州325035 [4]绍兴文理学院医学院护理系,浙江绍兴312000

出　　处：《温州医科大学学报》2017年第11期786-790,共5页Journal of Wenzhou Medical University

基　　金：浙江省公益性技术应用研究计划项目(Y2011c23123);温州市科技局科研基金资助项目(Y20120010;Y20130166)

摘　　要：目的:研究棉酚对糖尿病大鼠非酒精性脂肪性肝病(NAFLD)纤维化的影响及其可能机制。方法:雄性SD大鼠30只,随机均分成3组:正常对照(NC)组、2型糖尿病(T2DM)组、棉酚治疗(T2DMG)组。采用高脂饮食及低剂量链脲佐菌素(STZ)构建糖尿病大鼠模型,T2DMG组模型构建后用棉酚灌胃(15 mg·kg^(-1)·d^(-1) 灌胃4周,再按每周15 mg·kg^(-1)灌胃8周)。光镜及电镜下观察肝组织形态学改变;Masson染色观察肝组织纤维化病变;免疫组织化学检测肝组织α-平滑肌肌动蛋白(α-SMA)、11β-羟类固醇脱氢酶1(11β-HSD1)、糖皮质激素受体(GR)、核转录因子-κB(NF-κB)及转化生长因子β1(TGFβ1)蛋白的表达;RT-PCR法检测肝组织11β-HSD1、GR、NF-κB及TGFβ1 m RNA表达。结果:与NC组比较,T2DM组肝组织明显纤维化,α-SMA、11β-HSD1、GR、NF-κB、TGFβ1蛋白表达明显增多(P=0.001、0.004、0.001、0.001、0.002),GR、TGFβ1 m RNA表达明显增加(P=0.01、0.001);与T2DM组比较,T2DMG组肝纤维化病变明显减轻,肝组织α-SMA、11β-HSD1、GR、NF-κB、TGFβ1蛋白表达明显减少(P=0.009、0.031、0.002、0.009、0.027),11β-HSD1、GR、TGFβ1 m RNA表达明显减少(P=0.003、0.038、0.014)。结论:棉酚可以有效改善NAFLD相关肝纤维化病变,其机制可能是抑制肝脏11β-HSD1、GR、NF-κB、TGFβ1的表达。Objective： To investigate the effect of gossypol on nonalcoholic fatty liver disease （NAFLD） and its mechanism. Methods： Thirty male Sprague-Dawley rats were divided randomly into 3 groups： normal control （NC） group, type 2 diabetes mellitus （T2DM） group, type 2 diabetes mellitus treated with gossypol （T2DMG） group. After fed with a high-fat diet, the rats were injected with low-dose streptozotocin （STZ） intraperitoneally to induce type 2 diabetes mellitus. The T2DMG group were given 15 mg·kg-1·d-1 gossypol by gavage for 4 weeks, followed by 15 mg·kg-1·d-1 dose of gossypol every week for 8 weeks. The morphology of the liver was observed under light and transmission electronmicroscopy. Masson staining were used to observe the fibrosis of liver tissue. The protein expression of α-SMA, 11β-HSD1, GR, NF-κB and TGFβ1 were assayed by immunohistochemistry. The mRNA expression of 11β-HSD1, GR, NF-κB and TGF]31 from rats livers were assayed by semi-quantitative RT-PCR. Results： Compare with NC group, T2DM group hapatic fibrosis was obvious, α-SMA, 11β-HSD1, GR, NF-KB and TGFβ1 protein expression was significantly enhanced （P=0.001, 0.004, 0.001, 0.001, 0.002）, GR and TGFβ1 mRNA expression was significantly increased （P=0.01, 0.001）. Compare with T2DM group, T2DMG group liver fibrosis was significantly ameliorated, α-SMA, 11β-HSD1, GR, NF-κB and TGFβ1 expression was significantly decreased （P=-0.009, 0.03 l, 0.002, 0.009, 0.027）, 11β-HSD1, GR and TGFβ1 mRNA expression was significantly reduced （P=0.003, 0.038, 0.014）. Conclusion： Gossypol exerts the capacity to relieve hepatic fibrosis from NAFLD, inhibiting the expression of 11β-HSD1, GR and NF-κB, TGFβ1 may be involved in it.

关 键 词：肝纤维化 糖尿病 棉酚 11β-羟类固醇脱氢酶1 糖皮质激素受体 核转录因子-ΚB 转化生长因子Β1 

分 类 号：R363[医药卫生—病理学]