[1]沈友辉,杜斌.PAI-1引起2型糖尿病合并NAFLD小鼠肝脏炎性反应和纤维化的机制研究[J].国际内分泌代谢杂志,2021,41(02):110-115.[doi:10.3760/cma.j.cn121383-20200414-04038]
　Shen Youhui,Du Bin..Research of the effects of PAI-1 on inflammation and fibrosis in type 2 diabetic mice with NAFLD[J].International Journal of Endocrinology and Metabolism,2021,41(02):110-115.[doi:10.3760/cma.j.cn121383-20200414-04038]
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PAI-1引起2型糖尿病合并NAFLD小鼠肝脏炎性反应和纤维化的机制研究()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
41
期数:
2021年02期
页码:
110-115
栏目:
论著
出版日期:
2021-03-20

文章信息/Info

Title:
Research of the effects of PAI-1 on inflammation and fibrosis in type 2 diabetic mice with NAFLD
作者:
沈友辉; 杜斌
天津市泰达医院内窥镜科 300457
Author(s):
Shen Youhui;  Du Bin.
Department of Endoscopy, Tianjin TEDA Hospital, Tianjin 300457, China
关键词:
纤溶酶原激活物抑制剂-1;  2型糖尿病;  非酒精性脂肪性肝病;  纤维化;  炎症
Keywords:
Plasminogen activator inhibitor 1;  Type 2 diabetes mellitus;  Nonalcoholic fatty liver disease;  fibrosis;  inflammation
DOI:
10.3760/cma.j.cn121383-20200414-04038
摘要:
目的 探讨纤溶酶原激活物抑制剂-1(PAI-1)对2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)小鼠肝脏脂质沉积、炎性反应、纤维化等的影响。方法 以C57BL/KSJ-Lepdb雄性小鼠作为T2DM合并NAFLD组(db/db组),同周龄C57BKS db/m雄性小鼠作为对照组(db/m组)。采用苏木素-伊红染色、油红O染色等方法检测小鼠肝组织切片脂质沉积; 采用ELISA检测肝组织甘油三酯含量。以小鼠正常肝细胞NCTC1469作为研究对象,分为5组:对照组给予25 mmol/L葡萄糖(NG组)、高渗对照组给予25 mmol/L葡萄糖+25 mmol/L甘露醇(HMA组)、高糖高脂组给予50 mmol/L葡萄糖+0.75 mmol/L棕榈酸(HG+PA组)、高糖高脂+RNA干扰对照组(HG+PA+Si-NC组)用NC siRNA瞬时转染细胞并给予高糖高脂干预、高糖高脂+PAI-1沉默组(HG+PA+Si-PAI-1组)用PAI-1的siRNA瞬时转染细胞并给予高糖高脂干预。采用实时定量PCR和Western印迹方法检测炎性因子单核细胞趋化蛋白-1(MCP-1)、白细胞介素-1β(IL-1β)、肝纤维化相关指标转化生长因子-β(TGF-β)、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(Col Ⅰ)以及PAI-1的表达情况。结果 与db/m组相比,db/db组小鼠肝组织中出现明显脂质聚集和纤维组织增生,甘油三酯含量增加,且MCP-1、IL-1β、TGF-β、α-SMA、Col Ⅰ和PAI-1的mRNA和蛋白水平均明显上调(均P<0.05)。与NG组细胞相比,HG+PA组MCP-1、IL-1β、TGF-β、α-SMA、Col Ⅰ、PAI-1表达量均明显上调(均P<0.05); 与HG+PA组相比,HG+PA+si-PAI-1组PAI-1、MCP-1、IL-1β、TGF-β、α-SMA和Col Ⅰ等表达量均明显下调(均P<0.05)。结论 T2DM合并NAFLD小鼠模型肝组织中PAI-1表达明显增加,抑制PAI-1表达可明显改善肝组织炎性反应和纤维化水平。
Abstract:
Objective To investigate the effects of plasminogen activator inhibitor 1(PAI-1)on the hepatic lipid deposition, inflammatory reaction and fibrosis of type 2 diabetic mice with nonalcoholic fatty liver disease(NAFLD).Methods C57BL/KSJ lepdb mice were used as the model of T2DM combined with NAFLD(db/db group)and c57BKS db/m mice of the same age as the control group(db/m group). Hematoxylin eosin staining and oil red O staining were used to detect lipid droplets of the hepatic tissue sections of mice. NCTC1469 normal liver cells were divided into five groups: the control group(NG)treated with 25 mmol/L glucose in the medium, the HMA group treated with 25 mmol/L glucose and 25 mmol/L mannitol, the HG+PA group treated with 50 mmol/L glucose and 0.75 mmol/L PA, HG+PA+si-NC group treated with 50 mmol/L glucose and 0.75 mmol/L PA after the cells transiently transfected with NC siRNA, HG+PA+Si-PAI-1 group treated with 50 mmol/L glucose and 0.75 mmol/L PA after the cells transiently transfected with siRNA targeting PAI-1. The expression levels of MCP-1, IL-1β, TGF-β, α-SMA, Col Ⅰ and PAI-1 were detected by real-time quantitative PCR and Western blotting.Results Compared to the db/m mice, there were more accumulated lipid and fibroplasia in the hepatic tissues of db/db mice, and the mRNA and protein levels of MCP-1, IL-1β, TGF-β, α-SMA, Col Ⅰ and PAI-1 were increased significantly(P<0.05). Compared to the control group, the expression levels of MCP-1, IL-1β, TGF-β, α-SMA, Col Ⅰ and PAI-1 were also upregulated in HG+PA group(P<0.05). Compared to HG+PA group, the expression levels of PAI-1, MCP-1, IL-1β, TGF-β, α-SMA and Col Ⅰ were down-regulated in HG+PA+si-PAI-1 group(P<0.05).Conclusion The expression of PAI-1 was increased in T2DM mice combined with NAFLD. Inhibition of PAI-1 can significantly improve the inflammation and fibrosis.

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备注/Memo

备注/Memo:
通信作者:沈友辉,Email:shenyouhui@sina.com
更新日期/Last Update: 2021-03-20