摘要
【摘要】目的探讨枯否细胞在高脂诱导的肝脏胰岛素抵抗中的作用。方法将C57BIJ6J小鼠84只，分为普食组和高脂组，其中1组普食和1组高脂小鼠在喂养后1、2、4、8、12、16周行葡萄糖耐量检测，另外6组普食和6组高脂小鼠分别在上述时间处死取肝脏；Westernblot检测肝脏胰岛素受体底物1（IRS1）-ser307、蛋白激酶B（Akt）-ser473、核糖体蛋白s6激酶1（S6K1）一thr389、磷酸化c—Jun氨基末端激酶（p-JNK）表达；实时定量PCR检测肝脏炎性因子单核细胞趋化蛋白（MCP）-1、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1B、IL-10mRNA的表达。结果与普食喂养相比，高脂喂养小鼠1周后葡萄糖耐量检测显示葡萄糖代谢异常（P〈0．05），Westernblot显示高脂组肝脏IRSl-set307、S6KI—thr389（第4～16周）、p-JNK（2～16周）表达增强，Akt-ser473（8～16周）表达减弱，蛋白相对表达量与之一致（均P〈0．05）。第2～16周高脂组肝脏炎性因子MCP-1、TNF-12t．、IL-1BmRNA表达高于普食组（均P〈0．01），抗炎因子IL-10mRNA在第4．16周时低于普食组（均P〈0．01）。结论高脂饮食可能通过调节M1型枯否氏细胞分泌炎性因子和抑制M2型枯否细胞分泌抗炎因子在肝脏胰岛素抵抗中发挥作用。
Objective To explore the role of Kupffer cells in high fat diet induced hepatic insulin resistance. Meth- ods Eighty-four C57BL/6J mice were divided into two groups： normal chow （NC） group （7 subgroups） and high fat diet （HFD） group （7 subgroups）, Glucose tolerance tests were performed at feeding time of 1,2,4,8,12 and 16 weeks in one NC group and one HFD group. The mice livers at the same feeding time were obtained in other 6 NC groups and 6 HFD groups respectively. The expression levels of IRSl-ser307, Akt-ser473, S6Kl-thr389 and p-JNK were detected by Western blot as- say. The values of MCP-1, TNF-α, IL-1β and IL-10 mRNA were examined by qRT-PCR. Results Compared with NC group, the impaired glucose tolerance was found from the first week in HFD group （P 〈 0.05）. The hepatic expressions of IRSl-ser307, S6Kl-thr389 （4-16 weeks ） and p-JNK（2-16 weeks ） increased and Akt-ser473（8-16 weeks ）decreased in HFD group than those of NC group. The same results were gained by analysis of protein relative expression （all P 〈 0.05）. The hepatic pro-inflammatory factor MCP-1,TNF-c~ and IL-1 [3 mRNA expressions were higher in HFD group than those in NC group during 2-16 weeks （all P 〈 0.01）. The anti-inflammatory factor IL-10 mRNA was significantly lower in HFD group than that in NC group during 4-16 weeks （all P 〈 0.01）. Conclusion High fat diet maybe play a role in the hepatic insulin resistance by stimulating M1 Kupffer cells to secrete pro-inflammatory factor and inhibiting M2 Kupffer cells to se- crete anti-inflammatory factor.
出处
《天津医药》
CAS
北大核心
2013年第11期1106-1110,共5页
Tianjin Medical Journal
基金
天津市应用基础及前沿技术研究计划资助项目(项目编号:11JCYBJC11200)
