摘要
目的观察罗格列酮在盲肠结扎穿刺（CLP）大鼠肠道胰岛素信号中的作用。方法将sD大鼠随机分为CLP组（C组）、假手术组（S组）、罗格列酮组（R组）、罗格列酮＋胰岛素组（RI组）、CLP＋胰岛素组（cI组）和正常组（N组）。R、RI组在CLP前30min灌胃给予罗格列酮；RI、CI组在CLP后152min股静脉注射胰岛素；N组是正常大鼠。6组大鼠术前30min和术后每30min测空腹血糖，在155min取动脉血和近端空肠待检。测血和肠黏膜肿瘤坏死因子（TNF）-α浓度，行肠道组织病理学分析肠道损伤和炎症，免疫组织化学检测肠道胰岛素受体，同时检测胰岛素受体（IR）-β蛋白水平和胰岛素受体底物-1（IRS-1）蛋白表达及其酪氨酸磷酸化。结果罗格列酮可帮助控制CLP术后高血糖，明显降低血清和空肠黏膜中的TNF．仪水平；C、N组肠道损伤和炎症差异无统计学意义，IR-分布在肠黏膜的腔内侧；罗格列酮降低R组和RI组（比C组比较，P〈0．01）IR—B蛋白表达，C组IRS-1的酪氨酸磷酸化明显降低（比R组比较，P〈0．05），罗格列酮增加R组（比C组比较，P〈0．05）和胰岛素诱导的RI组（比C组比较，P〈0．01）的IRS-1酪氨酸磷酸化；罗格列酮治疗后，胰岛素明显增加IRS-I酪氨酸磷酸化（R比RI组比较，P〈0．01）；各组IRS．1总蛋白差异无统计学意义（P〉0．05）。结论CLP模型大鼠早期出现高血糖，空肠无明显炎症表现，肠黏膜胰岛素信号却是异常的；罗格列酮可控制CLP术后高血糖，并可降低全身和局部肿瘤坏死因子的浓度，改善空肠黏膜胰岛素信号。
Objective To investigate the role of rosiglitazone in intestine insulin signaling in rats after cecal ligation and puncture （CLP）. Methods The SD rats were randomly divided into CLP group （ C）, sham group （ S）, CLP ＋ rosiglitazone group （ R）, CLP ＋ rosiglitazone ＋ insulin group （ RI）, CLP ＋ insulin group （CI） and normal group （N）. The rats in R group were given rosiglitazone by intragastric ad- ministration at 30 min before CLP. The rats in RI and CI groups were injected with insulin through femoral vein at 152 min after CLP. The rats in N group received no administration. The glucose was measured at 30 min preoperatively and every 30 min postoperatively. At 155 min, artery blood was collected for determina- tion of plasma tumor necrosis factor （TNF） -or levels. The proximal jejunum was excised and jejunum TNF- c~ levels were also measured. Intestinal histological analysis and immunohistochemistry for insulin receptor were done at the indicated time points. In addition, IR-O protein, total protein and tyrosine phosphoryla- tion levels of IRS-1 were analyzed. Results Rosiglitazone significantly decreased production of TNF-ot in plasma and jejunum. No significant differences were observed between C and N groups about intestine mu- cosal injury and inflammation. The IR-~ subunits distributed on the intestinal mucosa. Rosiglitazone de- creased basic IR-[3 protein expression （P 〈 0. 01 vs C group）. Rosiglitazone increased baseline in R group （P 〈0. 05 vs C group） and insulin-induced Tyr phosphorylation of IRS-I in RI group （P 〈 0. 01 vs C group）. No significant differences were found in total protein of IRS-1 among groups （P 〉0. 05）. Conclu- sion No significant differences were observed about intestine mucosal injury and inflammation among groups at early phase, but intestinal insulin signaling was impaired. Rosiglitazone pretreatment could re- duce systematic and local production of TNF-αand improve intestinal insulin signaling.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2012年第2期226-229,共4页
Chinese Journal of Experimental Surgery
基金
教育部中央高校博士点基金，甘肃省卫生厅"陇原青年创新人才扶持计划"资助项目
