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益气健脾中药复方对糖尿病胃轻瘫大鼠胃动力的调控作用及机制
作者:郭海洋 李春雨 赵广明 付晓 
单位:121000 辽宁锦州 锦州医科大学附属第一医院中医针灸科(郭海洋、李春雨、付晓) 重症医学科(赵广明) 
关键词:益气健脾中药复方 糖尿病胃轻瘫 胃动力 
分类号:R631;R641
出版年,卷(期):页码:2019,44(8):659-665
摘要:

 [摘要]  目的  观察益气健脾中药复方对糖尿病胃轻瘫(DGP)大鼠胃动力的影响,并探讨其调控机制。方法  采用尾静脉注射STZ法结合高脂高糖、饥饱失常法建立大鼠DGP模型,4周后随机分为模型组(生理盐水10 ml/kg)、莫沙必利组(1.575 mg/kg)、中药高剂量组(益气健脾中药复方,5 g/kg)、中药低剂量组(益气健脾中药复方,1.25 g/kg), 另设正常动物为空白对照组(生理盐水10 ml/kg),每组10只。空白对照组、模型组给予生理盐水,莫沙必利组及中药高、低剂量组分别按以上浓度给予相应药物,1/d,灌胃4周。记录各组大鼠一般情况,监测体重、血糖、胃排空率和小肠推进率的变化;HE染色观察胃窦组织病理变化;ELISA检测血清胃泌素(GAS)及血浆胃动素(MTL)P物质(SP)含量;免疫组化法检测胃窦组织酪氨酸激酶(c-Kit)分布及表达情况;Western blotting法检测胃窦组织干细胞因子(SCF)c-Kit蛋白表达情况。结果  与空白对照组比较,模型组大鼠一般情况变差,体重减轻(P<0.01),血糖水平升高(P<0.01);与模型组比较,各给药组一般情况好转,体重增加(P<0.05),中药高、低剂量组血糖水平降低(P<0.05),以中药高剂量组改变最为明显。模型组大鼠胃排空率、小肠推进率均低于空白对照组(P<0.01),中药高剂量组、莫沙必利组胃排空率、小肠推进率均高于模型组(P<0.05)。与空白对照组比,模型组HE染色显示胃窦组织黏膜层腺体稀疏且排列紊乱,血管数量减少,各给药组胃窦组织黏膜层腺体及血管情况均较模型组改善,以中药高剂量组最为明显。模型组大鼠血清GAS,血浆MTLSP含量均低于空白对照组(P<0.01),各给药组血清GAS,血浆MTLSP含量均显著高于模型组(P<0.01)。模型组大鼠胃窦组织SCFc-Kit表达均低于空白对照组(P<0.01),各给药组胃窦组织SCF表达均高于模型组(P<0.05),以中药高剂量组最为显著(P<0.01),莫沙必利组、中药高剂量组c-Kit表达均高于模型组(P<0.05)结论  益气健脾中药复方可以改善DGP大鼠胃动力水平,且有一定的量效关系,其机制可能与促进GASMTLSP等胃肠激素分泌及调控胃窦组织SCFc-Kit蛋白表达有关。

 [Abstract]  Objective  To explore the potential mechanism of Yiqijianpi traditional Chinese medicine (TCM) compound treatment on gastric motility of diabetic gastroparesis (DGP) rats. Methods  Rats were treated with a single shot of STZ (tail vein injection) combined with high fat, high sugar, and irregular feeding methods for 4 weeks to induce DGP in these Rats. Then, they were randomized into the model group (normal saline 10 ml/kg), the mosapride group (mosapride 1.575 mg/kg), the high dose (5 g/kg), and the low dose TCM group (1.25 g/kg). In addition, normal rats were set as the control group (normal saline 10 ml/ kg). Each group of rats was intragastrically administered once a day for 4 weeks according to the dose and treatment indicated above. The general conditions were recorded. The changes in weight, blood glucose, gastric emptying rate, and intestinal propulsion rate were monitored. ELISA was used to detect serum levels of gastrin (GAS), plasma motilin (MTL) and substance P (SP). Immunohistochemistry was used to detect the distribution and expression of tyrosine kinase (c-Kit) in the gastric antrum. The expression of stem cell factor (SCF) and tyrosine kinase (c-Kit) were detected by Western blotting. HE staining was used to observe pathological changes of the gastric antrum. Results  Compared with the control group, rats induced with GDP showed deteriorated disease progress, such as lower body weight (P<0.01) and higher blood glucose levels (P<0.01). Compared with the model group, rats that treated with different drugs showed improved parameters, such as increased body (P<0.05). In addition, lower blood glucose levels were detected in high/low-dose TCM group (P<0.05), with dramatic improvement in the high dose TCM group. The gastric emptying rate and small intestine propulsion rate of the model group were lower than those in the control group (P<0.01). The gastric emptying rate and small intestine propulsion rate in the high dose of TCM and the mosapride group were higher than those in the model group (P<0.05). Compared with the control group, the HE staining of the model group showed gastric glands of the gastric antrum were sparse and disorderly arranged with reduced numbers of blood vessels. Compared with the model group, those improved in each drug-administered group with the best-improved parameters detected in the high dose TCM group. The levels of serum GAS, plasma MTL and SP in the model group were lower than that in the control group (P<0.01). The levels of serum GAS and plasma MTL and SP in each drug-administered group were significantly higher than the model group (P<0.01). The expressions of SCF and c-Kit in gastric antrum of the model group were lower than those in the control group (P<0.01). The expression of SCF in gastric antrum of each drug-administered group was higher than that in the model group (P<0.05), among which high dose of TCM group changed most significantly (P<0.01). The expression of c-Kit in the mosapride group and the high dose of TCM group was higher than that in the model group (all P<0.05). Conclusion  Yiqijianpi compound can improve the gastric motility of DGP rats in a dose-dependent manner. It is likely that Yiqijianpi compound can promote the secretion of GAS, MTL, SP and other gastrointestinal hormones, and regulate the expression of SCF and c-Kit proteins in the gastric antrum.

基金项目:
辽宁省自然科学基金(2013022014)
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