Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway
Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway
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DOI：
10.1016/j.biopha.2017.08.112
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发表时间：
2017-11-01
影响因子：
7.5
通讯作者：
Wang, Zhengang
中科院分区：
文献类型：
--
作者：
An, Xiaoxia;Long, Chunli;Wang, Zhengang
糖尿病胃轻瘫（DGP）是糖尿病（DM）的常见并发症。DGP临床症状多，治疗费用高，严重影响了患者的生活质量。然而，DGP的致病机制至今仍不清楚。本研究旨在探讨去甲乌药碱对DGP大鼠胃平滑肌细胞增殖和凋亡的影响。雄性SD大鼠腹腔注射链脲佐菌素（STZ）建立DGP大鼠模型。与健康对照组相比，模型组DGP指标c-kit水平明显降低，Gs α水平明显升高。而去甲乌药碱的加入明显抵消了STZ对c-kit和Gs α表达的影响。此外，去甲乌药碱改善胃排空能力下降。此外，模型组大鼠胃平滑肌细胞数量明显减少，细胞形态不规则。去甲乌药碱可减轻链脲佐菌素对胃平滑肌细胞数量和形态的损害。去甲乌药碱促进DGP模型大鼠胃平滑肌细胞增殖，抑制胃平滑肌细胞凋亡。进一步的研究表明去甲乌药碱通过激活β 2-AR/PI 3 K/AKT通路调节细胞增殖和凋亡。因此，我们的研究揭示去甲乌药碱通过β 2-AR/PI 3 K/AKT通路维持DGP大鼠胃平滑肌细胞的存活，为DGP的治疗提供了新的视角。
Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). The numerous clinical symptoms of DGP and the great cost on the treatment of DGP seriously lowered the patients' life quality. However, the pathogenic mechanism of DGP is still elusive till now. In this study, we aimed to explore the effect of higenamine on the proliferation and apoptosis of gastric smooth muscle cells (SMCs) in DGP rat model. The DGP rat model was built by intraperitoneal injection of Streptozotocin (STZ) into male Sprague-Dawley (SD) rats. Compared with the healthy control group, the level of DGP indicator c-kit was strongly suppressed and the level of Gs alpha was largely elevated in the STZ-induced model group. By contrast, the addition of higenamine obviously counteracted the effect of STZ on the expression of c-kit and Gs alpha. Besides that, higenamine improved the decreased emptying ability of the stomach. In addition, the number of gastric SMCs was strongly decreased and cell morphology became irregular in STZ-induced model group. The treatment of higenamine weakened the harm of STZ on the number and morphology of gastric SMCs. Beyond that, higenamine promoted gastric SMCs proliferation and inhibited gastric SMCs apoptosis in DGP model. Further research revealed that higenamine regulated cell proliferation and apoptosis via activating the beta 2-AR/PI3K/AKT pathway. Taken together, our research revealed that higenamine maintained the survival of gastric SMCs in DGP rat model via the beta 2-AR/PI3K/AKT pathway, providing a new sight for the treatment of DGP.