瘦素对大鼠肝纤维化及胞外信号调节激酶通路的影响  

Effect of ieptin on hepatic fibrosis and ERK signal transduction pathway in rats

作　　者：周光耀[1] 林巍[1] 金玲湘[1] 潘陈为[1] 诸葛璐[1] 郑毅[1] 方佩佩[1] 

机构地区：[1]温州医科大学附属第二医院感染内科,浙江省温州市325027

出　　处：《国际流行病学传染病学杂志》2014年第2期77-81,共5页International Journal of Epidemiology and Infectious Disease

基　　金：温州市科技局项目（Y20090296）

摘　　要：目的探讨瘦素调控大鼠肝纤维化的作用及ERK信号转导通路的机制。方法40只雄性SD大鼠，随机分为对照组、模型组、瘦素低剂量组和瘦素高剂量组，每组10只。对照组皮下和腹腔注射生理盐水，模型组、瘦素低剂量组和高剂量组在皮下注射40％四氯化碳蓖麻油溶液3mL／kg（首剂加倍）的同时分别腹腔注射生理盐水、瘦素2ns／kg和20ng／kg，每周2次，连续注射5周后处死取肝组织。采用苏木精一伊红（HE）、Masson染色，观察肝组织病理变化，利用Western印迹检测肝组织中p-ERKI^RKl、P—ERK2/ERK2、血管紧张素II（AngII）水平。结果HE和Masson染色显示，与对照组相比，模型组大鼠肝细胞胞质内充满脂滴空泡，间质内可见明显纤维组织增生；瘦素组大多数肝细胞轻度肿胀，可观察到脂滴空泡，血管周围纤维组织增生，并且瘦素20ng／kg组纤维化程度更严重。Western印迹结果显示，与对照组相比，模型组P—ERKl／ERKl、P．ERK2/ERK2、AngII蛋白水平均明显升高（t=11．62、5．16、4．55，P〈0．01）；与瘦素低剂量组相比，瘦素高剂量组p-ERK1/RKl、p-ERK2/ERK2、AngII蛋白水平明显升高（t=7．95、8．00、10．79，P〈0．01）。结论瘦素能够促进大鼠肝纤维化的形成，同时具有上调AngII和ERK信号转导通路相关蛋白的作用。Objective To study the effects of leptin on hepatic fibrosis and ERK signal transduction in rats. Methods Forty male SD rats were randomly divided into 4 groups： control group, model group, and two leptin groups （n=10 in each group）. Control groups were injected with saline subcutaneously and intraperitoneally; model group, 2 ng/kg leptin group, and 20 ng/kg leptin group were injected with normal saline, 2 ng/kg leptin and 20 ng/kg leptin, respectively, when they received subcutaneous injection of 40% carbon tetrachloride castor oil solution of 3 mL/kg （first doses doubled）, twice a week for 5 weeks. After that, rats were all sacrificed to obtain the liver tissue. The pathological changes of the liver tissue were observed with HE and Masson staining and the levels of p-ERK1/ERK1, p-ERK2/ERK2, and angiotension Ⅱ were detected by Western blot. Results HE and Masson staining results showed fat vacuoles in liver cells and fibrous tissue in interstitial area in model group and light edema, fat vacuoles in liver cells and fibrous tissue around blood vessels in leptin groups, and more severe fibrosis in 20 ng/kg leptin group. Compared with control group, the levels of p-ERK1/ERK1, p-ERK2/ERK2, and angiotension Ⅱ were elevated in model group （t=11.62, 5.16, 4.55, P〈0.01）. The levels of p-ERK1/ERK1, p- ERK2/ERK2, and angiotension Ⅱ in 20 ng/kg leptin group were higher than those in 2 ng/kg leptin group （t=7.95, 8.00, 10.79, P〈0.01）. Conclusions Leptin can promote the formation of liver fibrosis in rats by increasing the expression of angiotension Ⅱ and ERK signal pathway-related proteins.

关 键 词：瘦素 肝纤维化 ERK 信号转导 

分 类 号：R363[医药卫生—病理学]