阻塞性黄疸术后胰岛素抵抗与肠黏膜屏障破坏间的相关性

Correlation between post-operation insulin resistance and intestinal barrier dysfunction in obstructive jaundice rats

目的:探讨阻塞性黄疸(阻黄)术后胰岛素抵抗与肠黏膜屏障破坏间的相关性。方法:建立阻黄大鼠模型,术后给予胰高血糖素样肽2(GLP-2)和强化胰岛素治疗,分别于手术前1 d及手术后2、24、48 h和3、7 d采血,计算胰岛素抵抗指数,检测乳果糖/甘露醇(L/M)比值,ELISA法检测血清抵抗素样分子β(RELMβ)浓度,RT-PCR检测回肠组织内RELMβmRNA相对含量。结果:阻黄组术后3 d的胰岛素抵抗指数(10.1±1.8)和L/M比值(0.66±0.08)远高于其它时点(均P<0.05),两者呈明显正相关(r=0.86,P<0.05)。GLP-2组术后7 d的胰岛素抵抗指数降幅达37.0%,胰岛素组术后3 d的L/M降幅最大达46.7%(P<0.05)。阻黄组术后3 d血清RELMβ含量[(0.69±0.05)μg/L]和末端回肠上皮细胞内RELMβmRNA相对水平达到最高(1.40±0.06)。GLP-2组和胰岛素组的RELMβ浓度较阻黄组明显降低(P<0.05)。结论:阻黄术后胰岛素抵抗与肠黏膜屏障破坏间具有相关性,改善肠黏膜屏障和术后强化胰岛素治疗可以提升血清和组织内RELMβ含量。

AIM： To investigate the correlation between post-operation insulin resistance （IR） and intestinal barrier dysfunction in obstructive jaundice （OJ） rats. METHODS ： The rat model of OJ was set up. The rats were randoml divided into control group （sham operation）, OJ group, glucagon-like peptide 2 （GLP-2） group （challenged with GLP-2 by intraperitoneal injection） and insulin group （insulin subcutaneous injection）. Peripheral blood was collected 1 d before operation and 2 h, 24 h, 48 h, 3 d and 7 d after operation. The IR index and the ratio of lactulose/mannitol （L/M） were determined. The concentration of serum resistin-like molecule （RELM） β was detected by ELISA. The relative mRNA level of RELMβ in terminal ileum enteroeytes was measured by semi-quantitative RT-PCR. RESULTS： The IR index and the ratio of L/M in OJ group 3 d after operation were 10. 1 ± 1.8 and 0. 66 ±0. 08, respectively, which were higher than those at other time points （ all P 〈 0. 05）. The correlation coefficient between the changes of IR index and ratio of L/M was 0. 86 （ P 〈 0. 05）. The IR index in GLP-2 group descended by 37.0% 7 d after operation （7.33 ± 1.07 vs 4. 62 ± 0. 53, P 〈 0. 05）. The highest concentration of serum RELMβ was observed in OJ group 3 d after operation （0. 69 μg/L ±0. 05 μg/ L）. The relative mRNA level of RELMβ in terminal ileum enterocytes was also increased obviously. The expression of RELMβ was obviously decreased in GLP-2 group and insulin group. CONCLUSION： There is closed relationship between post-operation insulin resistance and intestinal barrier dysfunction. The RELMβ is the point of intersection. Enterocytes are not only the source of pest-operation insulin resistance but also the target organ.