和胃保津汤通过SCF/c-Kit与MEK/ERK通路改善糖尿病胃轻瘫OA
Hewei Baojin decoction allviates diabetic gastroparesis via SCF/c-Kit and MEK/ERK signaling pathways
目的 探究和胃保津汤对糖尿病胃轻瘫(DGP)大鼠的治疗作用及其机制.方法 60只雄性Wistar大鼠随机分为对照组、模型组、莫沙必利组(1.35 mg/kg)与和胃保津汤低、中、高剂量组(0.05,0.10,0.20 mL/kg),每组10只.除对照组外,其余5组采用链脲佐菌素联合高脂高糖不规则饮食诱导DGP模型,之后莫沙必利组大鼠给予1.35 mg/kg莫沙必利灌胃,和胃保津汤低、中、高剂量组大鼠分别给予0.05,0.10,0.20 mL/kg和胃保津汤灌胃.给药8周后,测量大鼠体质量、空腹血糖及胃排空率,ELISA法检测胃窦组织中胃动素(MTL)和胃泌素(GAS)含量,HE染色观察胃窦组织病理学变化,TUNEL染色观察胃窦细胞凋亡情况,免疫组化法检测胃窦组织中干细胞因子(SCF)、干细胞因子受体(c-Kit)、磷酸化丝裂原激活蛋白激酶激酶(p-MEK)、磷酸化细胞外信号调节激酶(p-ERK)阳性表达,Western blot法检测胃窦组织中SCF、c-Kit、p-MEK、MEK1/2、p-ERK、ERK1/2蛋白表达水平.结果 与对照组比较,模型组大鼠体质量、胃排空率、MTL及GAS含量下降,空腹血糖升高,胃窦组织明显损伤,细胞凋亡率升高,SCF、c-Kit、p-MEK、p-ERK阳性表达降低,SCF、c-Kit、p-MEK/MEK1/2、p-ERK/ERK1/2的蛋白表达水平均下调(均P<0.05).与模型组比较,莫沙必利组与和胃保津汤给药组大鼠体质量、胃排空率、MTL及GAS含量上升,空腹血糖降低,胃窦组织损伤得到改善,细胞凋亡减少,SCF、c-Kit、p-MEK、p-ERK阳性表达升高,以及SCF、c-Kit、p-MEK/MEK1/2、p-ERK/ERK1/2的蛋白表达水平也上调(均P<0.05),且和胃保津汤组呈现明显的剂量依赖性.结论 和胃保津汤能够改善DGP大鼠的胃肠道功能,其作用机制可能与调节SCF/c-Kit、MEK/ERK信号通路有关.
Objective To explore the efficacy and mechanism of Hewei Baojin decoction in diabetic gastroparesis(DGP)rats.Methods Sixty male Wistar rats were randomly divided into control group,model group,Mosapride group(1.35 mg/kg)and Hewei Baojin decoction low-,medium-and high-dose(0.05,0.10,0.20 mL/kg)groups(n=10 per group).Except for control group,the rats in the other five groups were treated with streptozotocin combined with an irregular high-fat and high-sugar diet to induce DGP model.Rats in Mosapride group were administered 1.35 mg/kg Mosapride by gavage,while those in Hewei Baojin decoction low-,medium-,and high-dose groups were administered the corresponding doses of the decoction by gavage,respectively.After 8 weeks of administration,body weight,fasting blood glucose and gastric emptying rate were measured.The levels of motilin(MTL)and gastrin(GAS)in gastric antrum tissue were detected by ELISA.Histopathological changes of gastric antrum tissues were observed by HE staining,and gastric antral cell apoptosis was observed by TUNEL staining.The positive expressions of stem cell factor(SCF),stem cell factor receptor(c-Kit),phosphorylated mitogen-activated protein kinase(p-MEK),and phosphorylated extracellular signal-regulated kinase(p-ERK)in gastric antrum tissue were detected by immunohistochemistry,and the protein expression levels of SCF,c-Kit,p-MEK,MEK1/2,p-ERK,and ERK1/2 in gastric antrum tissue were quantified by Western blot.Results Compared with control group,rats in model group exhibited decreased body weight,gastric emptying rate,MTL and GAS levels,along with increased fasting blood glucose,significant gastric antrum tissue damage,elevated apoptosis rate,reduced positive expression of SCF,c-Kit,p-MEK,and p-ERK,and down-regulated protein expres-sion levels of SCF,c-Kit,p-MEK/MEK1/2,and p-ERK/ERK1/2(all P<0.05).Compared with model group,the rats in Mosapride group and Hewei Baojin Decoction groups showed increased body weight,gastric emptying rate,MTL and GAS levels,along with decreased fasting blood glucose,ameliorated gastric antrum tissue damage,reduced apoptosis,enhanced positive expression of SCF,c-Kit,p-MEK,and p-ERK,and up-regulated protein expression levels of SCF,c-Kit,p-MEK/MEK1/2,and p-ERK/ERK1/2(all P<0.05).Furthermore,the effects of Hewei Baojin decoction group were observed in a dose-dependent manner.Conclusion Hewei Baojin decoc-tion can improve the gastrointestinal function in DGP rats through modulation of the SCF/c-Kit and MEK/ERK pathways.
贺红梅;邱玉萍;王芳;王齐有;邓德强
乌鲁木齐市中医医院内分泌科,乌鲁木齐 830000乌鲁木齐市中医医院针灸科乌鲁木齐市中医医院内分泌科,乌鲁木齐 830000乌鲁木齐市中医医院内分泌科,乌鲁木齐 830000乌鲁木齐市中医医院内分泌科,乌鲁木齐 830000
医药卫生
糖尿病胃轻瘫和胃保津汤胃窦组织大鼠成纤维细胞生长因子丝裂原激活蛋白激酶激酶
diabetic gastroparesisHewei Baojin decoctiongastric antrum tissueratsfibroblast growth factormitogen-activated protein kinase kinase
《山西医科大学学报》 2026 (3)
267-275,9
乌鲁木齐市中医药科技创新项目(ZYYMS-51)新疆维吾尔自治区卫生健康委员会"天山英才"医药卫生高层次人才培养计划项目(TSYC202301B167)
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