CAJ | 학술논문

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30 min灌胃给予罗格列酮；RI、CI组在CLP后152 min股静脉注射胰岛素；N组是正常大鼠.6组大鼠术前30 min和术后每30 min测空腹血糖,在155 min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-α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＜O.01)IR-β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-1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.
목적 관찰라격렬동재맹장결찰천자(CLP)대서장도이도소신호중적작용.방법 장SD대서수궤분위CLP조(C조)、가수술조(S조)、라격렬동조(R조)、라격렬동+이도소조(RI조)、CLP+이도소조(CI조)화정상조(N조).R、RI조재CLP전30 min관위급여라격렬동；RI、CI조재CLP후152 min고정맥주사이도소；N조시정상대서.6조대서술전30 min화술후매30 min측공복혈당,재155 min취동맥혈화근단공장대검.측혈화장점막종류배사인자(TNF)-α농도,행장도조직병이학분석장도손상화염증,면역조직화학검측장도이도소수체,동시검측이도소수체(IR)-β단백수평화이도소수체저물-1(IRS-1)단백표체급기락안산린산화.결과 라격렬동가방조공제CLP술후고혈당,명현강저혈청화공장점막중적TNF-α수평；C、N조장도손상화염증차이무통계학의의,IR-분포재장점막적강내측；라격렬동강저R조화RI조(비C조비교,P＜O.01)IR-β단백표체,C조IRS-1적락안산린산화명현강저(비R조비교,P＜0.05),라격렬동증가R조(비C조비교,P＜0.05)화이도소유도적RI조(비C조비교,P＜0.01)적IRS-1락안산린산화；라격렬동치료후,이도소명현증가IRS-1락안산린산화(R비RI조비교,P＜0.01)；각조IRS-1총단백차이무통계학의의(P＞0.05).결론 CLP모형대서조기출현고혈당,공장무명현염증표현,장점막이도소신호각시이상적；라격렬동가공제CLP술후고혈당,병가강저전신화국부종류배사인자적농도,개선공장점막이도소신호.
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 administration 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 determination of plasma tumor necrosis factor (TNF) -α levels.The proximal jejunum was excised and jejunum TNF-α levels were also measured.Intestinal histological analysis and immunohistochemistry for insulin receptor were done at the indicated time points.In addition,IR-β protein,total protein and tyrosine phosphorylation levels of IRS-1 were analyzed.Results Rosiglitazone significantly decreased production of TNF-α in plasma and jejunum.No significant differences were observed between C and N groups about intestine mucosal injury and inflammation.The IR-β subunits distributed on the intestinal mucosa.Rosiglitazone decreased basic IR-β 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-1 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 ).Conclusion 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 reduce systematic and local production of TNF-α and improve intestinal insulin signaling.