CAJ | 학술논문

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C57BL/6J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；Western blot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）-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）-1β、IL-10 mRNA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），Western blot显示高脂组肝脏IRS1-ser307、S6K1-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-α、IL-1βmRNA表达高于普食组（均P<0.01），抗炎因子IL-10 mRNA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。
목적：탐토고부세포재고지유도적간장이도소저항중적작용。방법장C57BL/6J소서84지，분위보식조화고지조，기중1조보식화1조고지소서재위양후1、2、4、8、12、16주행포도당내량검측，령외6조보식화6조고지소서분별재상술시간처사취간장；Western blot검측간장이도소수체저물1（IRS1）-ser307、단백격매B（Akt）-ser473、핵당체단백S6격매1（S6K1）-thr389、린산화c-Jun안기말단격매（p-JNK）표체；실시정량PCR검측간장염성인자단핵세포추화단백（MCP）-1、종류배사인자（TNF）-α、백세포개소（IL）-1β、IL-10 mRNA적표체。결과여보식위양상비，고지위양소서1주후포도당내량검측현시포도당대사이상（P<0.05），Western blot현시고지조간장IRS1-ser307、S6K1-thr389（제4~16주）、p-JNK（2~16주）표체증강，Akt-ser473（8~16주）표체감약，단백상대표체량여지일치（균P<0.05）。제2~16주고지조간장염성인자MCP-1、TNF-α、IL-1βmRNA표체고우보식조（균P<0.01），항염인자IL-10 mRNA재제4~16주시저우보식조（균P<0.01）。결론고지음식가능통과조절M1형고부씨세포분비염성인자화억제M2형고부세포분비항염인자재간장이도소저항중발휘작용。
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 IRS1-ser307, Akt-ser473, S6K1-thr389 and p-JNK were detected by Western blot as-say. The values of MCP-1,TNF-α,IL-1βand 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 IRS1-ser307, S6K1-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-αand IL-1βmRNA 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.