内质网应激在肝病性别差异形成中的影响及机制

汪杰; 何毅怀; 陈欢; 龙骏; 肖雪

doi:10.3969/j.issn.1001-5256.2019.12.023

内质网应激在肝病性别差异形成中的影响及机制

DOI: 10.3969/j.issn.1001-5256.2019.12.023

1. 遵义医科大学附属医院全科医学科
2. 遵义医科大学附属医院感染科

基金项目:

国家自然科学基金(81560110)；贵州省社会发展领域资金(黔科合支撑[2019]2803号)； 2017年贵州省卫生计生委科学技术基金(gzwjkj2017-1-021)；贵州省科技厅联合资金(黔科合LH字[2017]7093号)；

详细信息

中图分类号: R575
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出版历程
- 收稿日期: 2019-07-11
- 出版日期: 2019-12-20

Role and mechanism of action of endoplasmic reticulum stress in the formation of sex difference in liver diseases

Department of General Medicine,The Affiliated Hospital of Zunyi Medical University

Research funding:

摘要

摘要:
目的探讨内质网应激在肝病性别差异形成中的影响及机制。方法首先回顾性分析遵义医科大学附属医院2018年肝病门诊23 043例肝病患者及肝病科1110例肝病患者的性别分布情况;然后通过腹腔注射CCl4诱导急性肝损伤小鼠模型,验证肝损伤的性别差异,并进一步探讨内质网应激在肝损伤性别差异形成过程中的作用机制。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。计数资料多组间比较采用χ2检验。结果肝病门诊及肝病病房男性患者发病率明显高于女性患者,肝病门诊男女之比为1. 56∶1,肝病病房男女患者之比为1. 86∶1,差异有统计学意义（χ2=7. 517,P=0. 003）;在动物模型研究中,CCl4诱导小鼠急性肝损伤,雄性模型小鼠死亡率明显高于雌性模型小鼠（50%vs 30%,P<0. 05）,雄性模型小鼠血清ALT、TBil水平均明显高于雌性模型小鼠[（5767. 8±518. 8） U/L vs （4749. 5±378. 0） U/L,（6. 20±0. 88） mmol/L vs （4. 83±0. 57）mmol/L,P值均<0. 05],雄性模型小鼠...
- 肝疾病 /
- 内质网应激 /
- 性别比率 /
- 细胞凋亡
Abstract:
Objective To investigate the role and mechanism of endoplasmic reticulum stress in the formation of sex difference in liver diseases. Methods A retrospective analysis was performed to investigate the sex distribution of 23 043 patients with liver diseases in the outpatient service of hepatology and 1110 patients with liver diseases in Department of Hepatology in Zunyi Medical University in 2018. A mouse model of acute liver injury was established by intraperitoneal injection of carbon tetrachloride to confirm the sex difference of liver injury and investigate the mechanism of action of endoplasmic reticulum stress in the formation of sex difference in liver injury. A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. Results Among the patients in the outpatient service and the hospitalized patients,the male patients had a significantly higher incidence rate than the female patients,with a male/female ratio of 1. 56∶ 1 in the patients in the outpatient service and 1. 86 ∶ 1 in the hospitalized patients,and there was a significant difference between the two groups of patients( χ2= 7. 517,P = 0. 003). The animal model study showed that compared with the female mice with acute liver injury induced by carbon tetrachloride,the male mice had significantly higher death rate( 50% vs 30%,P < 0. 05),serum levels of alanine aminotransferase( 5767. 8 ± 518. 8 U/L vs 4749. 5 ± 378. 0 U/L,P < 0. 05) and total bilirubin( 6. 20 ± 0. 88 mmol/L vs4. 83 ± 0. 57 mmol/L,P < 0. 05),liver necrotic area( 47. 50% ± 4. 65% vs 38. 80% ± 5. 00%,P = 0. 043),and protein expression of the marker for hepatocyte apoptosis clea-caspase-3( 26. 00 ± 2. 11 vs 18. 40 ± 1. 54,P = 0. 042). Compared with the control mice,the model mice had significant increases in the expression of p-PERK,XBP1 s,P58 IPK,and CHOP in the liver( all P < 0. 05). Compared with the female model mice,the male model mice had significantly higher expression of XBP1 s( 25. 92 ± 2. 11 vs 15. 54 ± 1. 21,P = 0. 033),P58 IPK( 28. 60 ± 2. 43 vs 13. 56 ± 1. 13,P = 0. 026),and CHOP( 27. 15 ± 2. 61 vs 18. 18 ± 1. 81,P = 0. 038) and significantly lower expression of p-PERK( 16. 82 ± 0. 11 vs 22. 84 ± 0. 03,P = 0. 043) in the liver. Immunohistochemistry also showed that the male mice had significantly higher expression of CHOP than the female mice( 1. 00 ± 0. 11 vs 0. 62 ± 0. 03,P = 0. 032). Conclusion The uncoordinated activation of the endoplasmic reticulum stress signaling pathway may be involved in the formation of sex difference in liver diseases.
- liver disease /
- endoplasmic reticulum stress /
- sex ratio /
- apoptosis

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