HOXB7基因沉默表达对大鼠氧化应激及肝脏Nrf2表达的影响

Effects of HOXB7 gene silencing expression on oxidative stress and liver Nrf2 expression in rats with cirrhosis

目的探讨同源盒基因(HOX)B7基因沉默表达对大鼠氧化应激及肝脏NF-E2相关因子2(Nrf2)表达的影响。方法C57野生型雄性大鼠20只(对照组)与HOXB7基因沉默C57雄性大鼠20只(沉默组)分别采用皮下多点注射50%四氯化碳法建立肝硬化模型。记录两组建模后第4周、第8周大鼠体重;采用速率法检测两组建模后第4周、第8周血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)含量;采用化学比色法检测建模后第4周、第8周肝脏组织丙二醛(MDA)、总超氧化物歧化酶(T-SOD)和谷胱甘肽还原酶(GSH)含量;免疫组化分析SOD表达;记录建模后第8周的肝脏Nrf2 mRNA与蛋白表达水平。结果两组大鼠建模后主要表现为毛发不整、反应变迟缓,病理显示所有大鼠均建模成功。建模后第4周、第8周沉默组大鼠体重显著高于对照组(P<0.05)、血清AST、ALT、GGT值以及肝脏组织MDA含量均显著低于对照组(P<0.05),肝脏组织T-SOD和GSH含量显著高于对照组(P<0.05);沉默组建模后第8周的肝脏SOD表达阳性率显著高于对照组(P<0.05)。沉默组建模后第8周的肝脏Nrf2 mRNA与蛋白表达水平显著高于对照组(P<0.05)。结论HOXB7基因沉默表达能抑制大鼠氧化应激反应,提高肝脏SOD表达水平,有利于肝脏Nrf2的表达,从而能促进肝硬化大鼠恢复体重,降低肝功能损伤。

Objective To investigate the effects of homeobox(HOX)B7 gene silencing on oxidative stress and expression of NF-E2(Nrf2)in rat liver.Methods 20 cases of C57 wild-type male rats(control group)and 20 cases of HOXB7 gene-silencing C57 male rats(silent group)were established with cirrhosis model.Rats weight were recorded at 4 and 8 weeks after modeling in the two groups;serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and Gamma-glutamyl transpeptidase(GGT)content was detected at 4 and 8 weeks after feeding.The content of liver malondialdehyde(MDA),total superoxide dismutase(T-SOD)and glutathione reductase(GSH)were detected by chemical colorimetry;SOD expression was analyzed by immunohistochemistry;liver Nrf2 mRNA and protein expression levels were detected at 8 weeks after modeling.Results After modeled,the rats in two groups were showed mainly hair irregularities and slow response.Pathology showed that all rats were successfully modeled.At 4 and 8 weeks after modeling,the weight of the rats in the silent group was significantly higher than that in the control group(P<0.05),and the serum AST,ALT,GGT values,and MDA content in liver tissues were significantly lower than those in the control group(P<0.05).T-SOD and GSH contents in tissues were significantly higher than those in control group(P<0.05).The positive rate of SOD expression in the liver of the silent group were significantly higher than that of the control group at the 8 th week after modeling(P<0.05).The expression of Nrf2 mRNA and protein in the liver of the silent group were significantly higher than that of the control group at the 8th week after feeding(P<0.05).Conclusion The silenced expression of HOXB7 gene could inhibit oxidative stress in rats,increase the expression level of SOD in liver,and promote the expression of Nrf2 in liver,which could promote the recovery of body weight and reduce liver function damage in rats with liver cirrhosis.