茵陈蒿汤对酒精性肝纤维化大鼠肝组织Caspase-12通路的影响
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摘要
目的观察茵陈蒿汤对酒精性肝纤维化大鼠内质网应激的同型半胱氨酸(Hcy)-真核生物翻译起始因子(eIF2α)-Caspase-12通路引起的细胞凋亡的影响,探讨茵陈蒿汤防治酒精性肝纤维的作用机制。方法将40只SD大鼠随机分为空白组、模型组和茵陈蒿汤组,模型组和茵陈蒿汤组采用乙醇灌胃的方法复制酒精性肝纤维化大鼠模型,茵陈蒿汤组同时给予3. 5g/kg茵陈蒿汤灌胃,10周后处死动物,采用赖氏法检测各组大鼠血清丙氨酸氨基转移酶(ALT)和门冬氨酸氨基转移酶(AST)水平,采用HE和Masson三色染色观察各组大鼠肝脏组织病理学表现,采用Real-Time PCR法检测各组大鼠肝脏组织中GRP78、eIF-2α、Caspase-12mRNA表达情况。结果模型组大鼠血清ALT、AST水平明显高于空白组(P均<0. 05),茵陈蒿汤组大鼠血清ALT、AST水平均明显低于模型组(P均<0. 05)。肝脏组织病理学显示,模型组大鼠出现明显肝纤维化表现,茵陈蒿汤组大鼠肝纤维化程度较模型组明显减轻。模型组大鼠肝脏组织中GRP78、eIF-2α、Caspase-12mRNA表达水平均明显高于空白组(P均<0. 05),茵陈蒿汤组大鼠肝脏组织中GRP78、eIF-2α、Caspase-12mRNA表达水平均明显低于模型组(P均<0. 05)。结论茵陈蒿汤抑制GRP78、eIF-2α、Caspase-12的活性可能是其抗酒精性肝纤维化的作用机制之一。
Objective It is to observe the effect of Yinchenhao Decoction on cell apoptosis induced by homocysteine(Hcy)-eukaryotic translation initiation factor(e IF2α)-Caspase-12 pathway in endoplasmic reticulum stress in alcoholic liver fibrosis rats,and to explore the mechanism of Yinchenhao Decoction in the prevention and treatment of alcoholic liver fiber. Methods Forty SD rats were randomly divided into blank group,model group and Yinchenhao decoction group. The model group and Yinchenhao decoction group were used to replicate the rat model of alcoholic liver fibrosis by ethanol gavage. The rats in Yinchenhao Decoction group were given 3. 5 g/kg Yinchenhao Decoction by gavage at the same time. After 10 weeks,the animals were sacrificed. The levels of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by Reitman method. The liver histopathology was observed by HE and Masson three-color staining. The expression of GRP78,e IF-2α and Caspase-12 mRNA in liver tissues of each group were detected by Real-Time PCR. Results The levels of serum ALT and AST in the model group were significantly higher than those in the blank group(P < 0. 05). The serum ALT and AST levels in the Yinchenhao Decoction group were significantly lower than those in the model group(P < 0. 05). Liver histopathology showed that the model group had obvious liver fibrosis,and the degree of liver fibrosis in the Yinchenhao Decoction group was significantly relieved compared with the model group. The expression levels of GRP78,e IF-2α and Caspase-12 mRNA in the liver tissues of the model group were significantly higher than those in the blank group(P < 0. 05),while these indexes in Yinchenhao Decoction group were significantly lower than that of the model group(P < 0. 05). Conclusion Yinchenhao Decoction could inhibit the activity of GRP78,e IF-2α and Caspase-12,and this may be one of the mechanisms of its anti-alcoholic liver fibrosis.
Objective It is to observe the effect of Yinchenhao Decoction on cell apoptosis induced by homocysteine(Hcy)-eukaryotic translation initiation factor(e IF2α)-Caspase-12 pathway in endoplasmic reticulum stress in alcoholic liver fibrosis rats,and to explore the mechanism of Yinchenhao Decoction in the prevention and treatment of alcoholic liver fiber. Methods Forty SD rats were randomly divided into blank group,model group and Yinchenhao decoction group. The model group and Yinchenhao decoction group were used to replicate the rat model of alcoholic liver fibrosis by ethanol gavage. The rats in Yinchenhao Decoction group were given 3. 5 g/kg Yinchenhao Decoction by gavage at the same time. After 10 weeks,the animals were sacrificed. The levels of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by Reitman method. The liver histopathology was observed by HE and Masson three-color staining. The expression of GRP78,e IF-2α and Caspase-12 mRNA in liver tissues of each group were detected by Real-Time PCR. Results The levels of serum ALT and AST in the model group were significantly higher than those in the blank group(P < 0. 05). The serum ALT and AST levels in the Yinchenhao Decoction group were significantly lower than those in the model group(P < 0. 05). Liver histopathology showed that the model group had obvious liver fibrosis,and the degree of liver fibrosis in the Yinchenhao Decoction group was significantly relieved compared with the model group. The expression levels of GRP78,e IF-2α and Caspase-12 mRNA in the liver tissues of the model group were significantly higher than those in the blank group(P < 0. 05),while these indexes in Yinchenhao Decoction group were significantly lower than that of the model group(P < 0. 05). Conclusion Yinchenhao Decoction could inhibit the activity of GRP78,e IF-2α and Caspase-12,and this may be one of the mechanisms of its anti-alcoholic liver fibrosis.
引文
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[7]李木松,张贵贤,魏媛媛,等.茵陈蒿汤对胆汁淤积性肝纤维化大鼠内质网应激PERK通路的影响[J].中国中医药科技,2016,23(5):535-538
[8]李木松,张贵贤,魏媛媛,等.茵陈蒿汤对肝纤维化大鼠肝组织内质网应激caspase-12通路的影响[J].世界中医药,2016,11(9):1839-1841
[9]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术(中医药现代化),2016,18(9):1507-1514
[10]中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.酒精性肝病防治指南(2018年更新版)[J].实用肝脏病杂志,2018,21(2):170-176
[11]窦志华,罗琳,孟萍,顾薇.茵陈蒿汤不同方剂配伍对黄疸模型大鼠肝功能的影响比较[J].南通大学学报:医学版,2017,37(1):17-20
[12]姜英凤,韩莉,石祥奎,等.茵陈蒿汤加减方对母子ABO血型不合所致新生儿病理性黄疸干预作用及安全性分析[J].齐齐哈尔医学院学报,2017,38(13):1520-1522
[13]李木松,张贵贤,魏媛媛,等.内质网应激caspase-12通路在大鼠胆汁淤积性肝纤维化模型中的作用研究[J].山西医药杂志,2016,45(6):642-643
[2]陈士林,孟晓丹,王炳元,等.辽宁省部分城市酒精性肝病流行现状调查[J].实用肝脏病杂志,2010,13(6):428-430; 435
[3] Wang H,Ma L,Yin Q,et al. Prevalence of alcoholic liver disease and its association with socioeconomic status in north-eastern China[J]. Alcohol Clin Exp Res,2014,38(4):1035-1041
[4] Qiu P,Li X,Kong DS,et al. Research progress on pathogenesis of alcoholic liver disease[J]. Chin Pharmacol Bull,2014,30(2):160-163
[5] Li RJ,He KL,Li X,et al. Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2α[J]. Mol Med Rep,2015,12(1):1043-1049
[6]吴东辉,于红.茵陈蒿汤加减治疗肝炎引起的黄疸的临床观察[J].光明中医,2018,33(1):71-72
[7]李木松,张贵贤,魏媛媛,等.茵陈蒿汤对胆汁淤积性肝纤维化大鼠内质网应激PERK通路的影响[J].中国中医药科技,2016,23(5):535-538
[8]李木松,张贵贤,魏媛媛,等.茵陈蒿汤对肝纤维化大鼠肝组织内质网应激caspase-12通路的影响[J].世界中医药,2016,11(9):1839-1841
[9]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术(中医药现代化),2016,18(9):1507-1514
[10]中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.酒精性肝病防治指南(2018年更新版)[J].实用肝脏病杂志,2018,21(2):170-176
[11]窦志华,罗琳,孟萍,顾薇.茵陈蒿汤不同方剂配伍对黄疸模型大鼠肝功能的影响比较[J].南通大学学报:医学版,2017,37(1):17-20
[12]姜英凤,韩莉,石祥奎,等.茵陈蒿汤加减方对母子ABO血型不合所致新生儿病理性黄疸干预作用及安全性分析[J].齐齐哈尔医学院学报,2017,38(13):1520-1522
[13]李木松,张贵贤,魏媛媛,等.内质网应激caspase-12通路在大鼠胆汁淤积性肝纤维化模型中的作用研究[J].山西医药杂志,2016,45(6):642-643