PTP1B及瘦素信号通路在奥曲肽抗大鼠肝纤维化中的作用  

Octriotide promotes PTP1B expression to protect carbon tetrachloride-induced hepatic fibrogenesis rats

作　　者：陈元淦 张超[1] 李方跃[1] 牛森森[1] 

机构地区：[1]安徽医科大学第一附属医院肝胆胰外科一病区,合肥230022

出　　处：《安徽医科大学学报》2016年第4期501-505,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省教育厅自然科学基金(编号:KJ2014A117)

摘　　要：目的研究蛋白酪氨酸磷酸酶1B(PTP1B)在奥曲肽(OCT)治疗大鼠肝纤维化过程中的作用机制,及其对瘦素和JAK2-STAT3信号通路的影响。方法将大鼠随机分为:空白组、OCT组、模型组。模型组和OCT组采用皮下注射四氯化碳(CCI4)法建立肝纤维化模型。饲养8周后,采集标本,全自动生化分析仪测定血清肝脏生化指标:总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及大鼠血清白蛋白(ALB)。ELISA法测定瘦素水平,HE染色观察肝脏病理,免疫组化法检测肝组织瘦素及瘦素受体(Ob-Rb)的表达,碱水解法测定肝脏中羟脯氨酸(Hyp)含量。Western blot法检测肝组织内PTP1 B、JAK2、STAT3、pJAK2、p-STAT3的表达。结果与空白组比较,模型组和OCT组大鼠血清中TBIL、ALT、AST水平上升(P<0.05),ALB水平明显降低(P<0.05),血清瘦素、肝组织内瘦素及瘦素受体表达增加(P<0.001)。肝组织中Hyp含量明显升高(P<0.05)。模型组及OCT组JAK2、STAT3磷酸化水平较空白组升高(P<0.001)。OCT组与模型组比较,肝脏生化指标改善明显,病理改变较轻,血清瘦素含量减少(P<0.05),肝组织内瘦素、Ob-Rb及Hyp含量降低(P<0.05),JAK2、STAT3磷酸化水平较模型组均有降低(P<0.05),而PTP1B表达增加(P<0.001)。结论应用OCT能一定程度上减轻大鼠肝维化程度,减轻肝脏损伤。推测其机制是OCT通过上阔PTP1B,抑制了瘦素及JAK2/STAT3信号通路的促肝纤维化效应,最终达到抗肝纤维化的目的 。Objective To investigate the mechanisms of octriotide （OCT） protecting carbon tetrachloride-induced hepatic fibrogenesis rats and the effects of protein tyrosine phosphatase 1B （PTP1B ） on leptin and JAK2/STAT3 signaling. Methods Adult male SD rats were divided into three groups ： control, OCT and model group. The liver fibrosis models were induced with carbon tetrachloride （CCl4 ）. The levels of total bilirubin（ TBIL）, alanine amin- otransferase （ALT）, aspartate aminotransferase （AST）, serum albumin（ALB） and leptin in serum and Hyp in liver were tested and histopathology changes were observed. Leptin and obese receptor （Ob-Rb） expressions were ob- served by immunohistoehemical staining. The expressions of the phosphorylation of Janus kinase2 （JAK2）, signal transducers and activators of transcription 3 （ STAT3 ） and PTP1B were tested by Western blot. Results In model and OCT group, compared with the control group, the levels of TBIL, ALT, AST and leptin in serum increased and serum ALB decreased（ P 〈0. 05 ）. Compared with the control group, in model and OCT group, the expressions of Hyp, p-JAK2, p-STAT3, leptin and Ob-Rb in liver increased （P 〈 0. 05 ）. In OCT group, with lower leptin, OB- Rb and Hyp expression, the injury of hepatic histopathology was less serious than that in model group. In model group, the expressions of p-JAK2 and p-STAT3 rose more evidently than OCT group （ P 〈 0. 05 ）, while PTP1B ex- pressions were lower（P 〈 0. 001 ）. Conclusion OCT can ease the CC14-induced hepatic injury and relieve liver fi- brosis. OCT dampens leptin signaling by stimulating PTP1 B expression, which is a negative regulator of JAK2/ STAT3, and thus inhibits liver fibrosis.

关 键 词：瘦素 奥曲肽 蛋白酪氨酸磷酸酶1B JAK2/STAT3 

分 类 号：R575.2[医药卫生—消化系统]