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胰升血糖素样肽-1对肝切除后肝细胞胞浆游离钙影响的实验研究

The influence of glucagon-like peptide-1 on cytosolic free calcium ion concentration in isolated rat hepatocytes after hepatectomy
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摘要 目的探讨胰升血糖素样肽-1(GLP-1)对肝切除后肝细胞胞浆游离钙的影响。方法将大鼠随机分2组,A组不切肝,B组切肝65%。于术后第1,3,5天收集血标本5mL测定血糖、GLP-1、胰岛素(In)和胰升血糖素(G1)。同时用酶法分离制备肝细胞悬液。以Fura-2/AM荧光指示剂,用荧光分光光度仪检测肝切除后肝细胞的荧光强度及GLP-1对荧光强度的影响。结果B组肝切除术后血糖明显增高(P<0.05),血浆GLP-1也明显高于A组(P<0.001),尤以术后第1天更显著;In则明显下降(P<0.001),而G1手术后升高,但差异无显著性(P>0.05),术后In/GL值明显下降(P<0.05)。所测正常肝细胞[Ca2+]i为(707.46±122.59)nmol/L,肝切除术后第1,3,5天肝细胞[Ca2+]i较正常肝细胞略降低(P>0.05);加入GLP-1后肝细胞[Ca2+]i略有升高(P>0.05)。结论大鼠肝切除术后存在明显胰岛素抵抗,主要系因胰岛素水平明显下降,致In/G1值也明显降低的结果;GLP-1的拟胰岛素作用并非通过增加肝细胞[Ca2+]in而实现的。 Objective To investigate the effect of glucagon-like peptide-1 ( GLP-1 ) on cytosolic free calcium ion concentration ( [ Ca^2+ ] i ) in isolated rat hepatocytes after hepatectomy. Methods The rats were allocated randomly to two groups: The rats of group one did not undergo hepatectomy. The rats of group two had 65 % liver resection. The blood specimen taken from vena cava was mensurated for glucose, insulin, glucagon, and glucagon-like peptide-1 ( GLP-1 ) on the first, third and fifth day after hepatectomy. The [ Ca^2+ ] i in isolated rat hepatocytes was investigated by using fura-2 fluoresence, and then, in vitro, the effect of GLP-1 on the [ Ca^2+ ] i in hepatocytes was investigated in 2 groups. Results The blood glucose value in group two was significantly higher than that in group one after operation ( P 〈 0.05 ) , especially on the first day. The plasma GLP-1 value was also significantly higher than that of group one ( P 〈 0. 001 ). The level of serum insulin was decreased obviously ( P 〈 0. 001 ) , while the value of glucagon was increased, but not significantly, which led to reduction of the ratio of insulin to glucagon. The [ Ca^2+ ] i in hepatocytes on the first, third and fifth day after hepatectomy was decreased slightly ( P 〉 0.05 ) compared with that of group one. In vitro, GLP-1 produced a slightly increase in the [ Ca^2+ ] i in hepatocytes (P 〉0.05 ). Conclusions After hepatectomy, in rats is associated with an obvious insulin resistance,mainly due to the level of serum insulin was obviously decreased ( P 〈 0.001 ) , and the value of glucagon was increased, which led to reduced ratio of insulin to glucagon. GLP-1 is insulinomimetic upon glucose metabolism in hepatic tissue, which acting through specific receptors is not associated to [ Ca^2+ ] i increase.
出处 《中国普通外科杂志》 CAS CSCD 2007年第7期653-656,共4页 China Journal of General Surgery
基金 国家自然科学基金资助项目(39600143)
关键词 肝切除术 肝细胞/代谢 胰升血糖素样肽-1 胞浆游离钙 Hepatectomy Hepatocytes/metab Glucagon-like Peptide-1 Cytosolic Free Calcium IonConcentration
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