H_2S在PI3K/AKT/GSK-3β信号通路中对大鼠肝纤维化的影响  

Hydrogen sulfide delays process of experimental hepatic fibrosis in rats through PI3K/AKT/GSK-3β signal pathway

作　　者：张传峰[1] 岳雅伦 张宁[2] 宋丽秀[2] 赵强[1] 杨新疆[1] 陈卫刚[2] 郑勇[2] 

机构地区：[1]新疆石河子大学医学院,新疆维吾尔自治区石河子市832002 [2]新疆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

出　　处：《世界华人消化杂志》2014年第23期3445-3451,共7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:探讨硫化氢(sodium hydrogen,H2S)在磷酯酰肌醇3激酶(phosphoinositide-3-kinase,PI3K)/AKT/糖原合成酶激酶-3β(glycogensynthesis kinase-3β,GSK-3β)信号通路中对大鼠肝纤维化的影响.方法:选择硫氢化钠(sodium hydrogen,NaHS)作为H2S的供体,LY294002作为PI3K/AKT的特异性阻断剂.将48只♀SD大鼠随机分为6组:正常对照组(N组)8只、肝纤维化组(C组)8只、肝纤维化+DMSO溶剂对照组(D组)8只、肝纤维化+PI3K/AKT信号通路抑制剂LY294002组(LY组)8只、肝纤维化+NaHS组(S组)8只、肝纤维化+LY294002+NaHS组(LS组)8只,采用四氯化碳复合因素复制肝纤维化模型,干预剂以腹腔注射,1次/d,共注射12次.具体如下:(1)N组和C组:腹腔注射0.9%氯化钠注射液,剂量为6 mL/kg体质量;(2)D组:腹腔注射2‰DMSO溶液,剂量为6 mL/kg体质量;(3)LY组:腹腔注射LY294002溶液,剂量为0.3 mg/(kg?d);(4)S组:腹腔注射NaHS溶液,剂量为56μmol/(kg?d);(5)LS组,同时注射LY294002溶液和NaHS溶液,剂量同LY组和S组,将两种溶液于腹腔的两侧注入,而非同侧腹腔注射.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,应用Western blot法检测肝脏中GSK-3β表达.结果:NaHS干预组和肝硬化组相比,GSK-3β表达下降(P<0.01),与肝纤维化分期结果一致(P<0.01).与LY294002+NaHS干预组相比较,GSK-3β在LY294002干预组中表达增高(P<0.01);在NaHS干预组中表达下降(P<0.01),与肝纤维化分期结果一致(P<0.01).结论:H2S可以通过PI3K/AKT信号通路抑制GSK-3β表达,并延缓大鼠肝纤维化过程,阻碍肝纤维化的发展.AIM： To investigate whether hydrogen sulfide（H2S） delays the process of experimental hepaticfibrosis through the phosphoinositide-3-kinase（PI3K）/AKT/glycogen synthesis kinase-3β（GSK-3β） signal pathway.METHODS： Sodium hydrogen sulphide（NaHS） was selected as the donor of H2 S and LY294002 as the specific blocker of PI3K/AKT signal-ing.Forty-eight female SD rats were divided randomly and equally into 6 groups： a normal group（N group）,a liver fibrosis group（C group）,a DMSO group（D group）,an LY294002 intervention group（LY group）,a NaHS inter-vention group（S group）,and an LY294002 ＋ NaHS intervention group（LS group）.Liver fibrosis was induced in rats with carbon tet-rachloride.The above agents were given by intraperitoneal injection,once a day for a total of 12 times.For the N group and C group,0.9% sodium chloride injection（6 mL/kg of body mass） was intraperitoneally injected; for the D group,2‰ DMSO（6 mL/kg of body mass） was given; for the LY group,LY294002 solution 0.3 mg/（kg？d） was given; for the S group,NaHS solution 56 μmol/（kg？d） was given; for the LS group,NaHS and LY294002 were given si-multaneously.Fibrosis was staged using histo-pathological methods.The expression of GSK-3β was detected by Western blot.RESULTS： Compared to the C group,the stage of fibrosis was downgraded（P〈0.01） and the expression of GSK-3β was decreased（P〈0.01） in the S group.Compared to the LS group,the expression of GSK-3β was increased in the LY group（P〈0.01） and was decreased in the S group（P〈0.01）,and the stage of fibrosis in the S group was also downgraded（P〈0.01）.CONCLUSION： H2 S can decrease the expression of GSK-3β and delay the process of liver fibrosis in rats through the PI3K/AKT/GSK-3β signal pathway.

关 键 词：硫化氢 肝纤维化 PI3K/AKT GSK-3Β 

分 类 号：R575[医药卫生—消化系统]