Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway

Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway
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长脉冲胃电刺激通过IGF-1信号通路保护糖尿病大鼠Cajal间质细胞

DOI:
10.3748/wjg.v22.i23.5353
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发表时间:
2016-06-21
影响因子:
4.3
通讯作者:
Hou, Xiao-Hua
Hou, Xiao-Hua
中科院分区:
医学2区
文献类型:
--
作者:
Li, Hai;Chen, Yan;Hou, Xiao-Hua

文献摘要

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目的:探讨不同参数胃电刺激(GES)对链脲佐菌素诱导的糖尿病大鼠Cajal间质细胞(ICCs)及胰岛素样生长因子1(IGF-1)信号通路变化的影响。方法:将雄性大鼠随机分为对照组、糖尿病(DM)、糖尿病假GES(DM+SGES)、糖尿病GES1组。 (5.5 cpm,100 ms,4 mA)(DM + GES1),糖尿病组 GES2(5.5 cpm,300 ms,4 mA)(DM + GES2)和糖尿病组 GES3(5.5 cpm,550 ms,2 mA)(DM + GES3)组。使用蛋白质印迹分析评估胃窦中c-kit、M-SCF和IGF-1受体的表达水平。使用c-kit免疫标记观察ICC的分布,使用α-SMA和IGF-1R抗体鉴定平滑肌细胞和IGF-1受体。采用酶联免疫吸附法检测血清IGF-1水平。结果:DM组胃排空延迟,但所有GES组胃排空均有所改善,尤其是GES2组。 DM组中c-kit、M-SCF和IGF-1R的表达水平降低,但所有GES组中c-kit、M-SCF和IGF-1R的表达水平均升高。与DM组相比,所有GES组中观察到更多的ICC(c-kit(+))和平滑肌细胞(α-SMA(+)/IGF-1R(+))。 DM组IGF-1平均水平明显下降,但在所有GES组中均上调,尤其是GES2组。结论:结果提示长脉冲GES促进ICCs再生。 IGF-1 信号通路可能参与这一过程的潜在机制,从而改善胃排空。
AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats.METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using alpha-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay.RESULTS: Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (alpha-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group.CONCLUSION: The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.