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刺猬信号通路在氟中毒大鼠肝脏中表达及意义

DOI: 10.11847/zgggws2015-31-09-16, PP. 1162-1166

Keywords: 氟中毒,肝损伤,刺猬(Hh)信号通路,氧化应激

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Abstract:

?目的探讨刺猬信号通路(Hh)在慢性氟中毒大鼠肝脏损伤中作用及机制。方法选择健康成年SD大鼠36只,按体重随机分为对照组、低、高剂量染氟组(饮水中含氟量分别为5、50mg/L),每组12只(雌雄各半),饲养6个月后检测大鼠尿氟、骨氟含量;应用自动生化分析仪检测大鼠肝功能;免疫组织化学(IHC)、Westernblot和逆转录PCR(RT-PCR)法检测大鼠肝脏组织中印度刺猬蛋白(Ihh)、跨膜蛋白(Smo)、胶质瘤相关癌基因(Gli1)蛋白和mRNA表达;试剂盒法检测肝组织中总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-Px)和谷氨酰胺合成酶(GS)活力及脂质过氧化物(LPO)含量。结果与对照组比较,染氟组大鼠尿氟、骨氟含量、高剂量染氟组大鼠血清谷丙转氨酶、谷草转氨酶活性[分别为(73.42±6.98)、(161.08±8.59)U/L]明显增加,高剂量染氟组大鼠肝组织中Ihh、Smo、Gli1蛋白和mRNA的表达[分别为(71.41±4.18)、(83.83±5.26)、(81.14±25.44)及(1.20±0.17)、(3.13±0.19)、(5.35±0.52)]明显增加,高剂量染氟组大鼠肝组织中T-SOD、GSH-Px、GS活性[(5.08±0.64)、(5.53±0.83)、(19.22±1.84)U/mgprot]明显降低,LPO含量[(10.29±1.81)μmol/gprot]升高,差异均有统计学意义(P<0.05)。结论Hh信号通路与氧化应激可能共同参与慢性氟中毒所致肝脏损伤发病过程。

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