摘要
目的探讨半夏泻心汤对糖尿病胃轻瘫(DGP)小鼠胃排空的影响及可能作用机制。方法30只雌性db/db小鼠为自发型2型糖尿病小鼠,使用高脂高糖饲料适应性喂养1周后,通过13C辛酸呼吸检测法区分DGP小鼠[胃半排空时间(T1/2)连续两次>129 min]和非DGP小鼠,将非DGP小鼠5只设为2型糖尿病对照组,DGP小鼠再随机分为糖尿病胃轻瘫模型组、甲氧氯普胺组和半夏泻心汤低、中、高剂量组,每组5只。各组小鼠均给予250 mg/(kg·d)二甲双胍基础用药,甲氧氯普胺组在基础用药上加10 mg/(kg·d)甲氧氯普胺,半夏泻心汤低、中、高剂量组分别加用750、1500、3000 mg/(kg·d)半夏泻心汤灌胃,各组连续灌胃8周。8周后各组小鼠检测空腹血糖并进行腹腔注射糖耐量试验,使用糖耐量曲线下面积评价小鼠葡萄糖敏感性;使用13C呼吸试验计算T1/2以评估小鼠胃动力;检测胃组织Cajal间质细胞(ICCs)及其干细胞(ICC-SC)数量、胃组织晚期糖基化终末产物(AGEs)含量及晚期糖基化终产物受体(RAGE)、神经元型一氧化氮合酶(nNOS)蛋白表达。结果与2型糖尿病对照组相比,糖尿病胃轻瘫模型组小鼠空腹血糖、糖耐量曲线下面积、T1/2均升高,胃组织中ICCs及ICC-SC数量明显减少,AGEs含量及RAGE蛋白表达升高,nNOS蛋白表达降低(P<0.01)。与糖尿病胃轻瘫模型组和甲氧氯普胺组相比,半夏泻心汤中、高剂量组小鼠的空腹血糖和糖耐量曲线下面积均显著降低,胃组织中ICCs以及ICC-SC数量显著增加,AGEs含量和RAGE蛋白表达降低,nNOS蛋白表达上升(P<0.01)。半夏泻心汤高剂量组较甲氧氯普胺组T1/2缩短(P<0.01)。与半夏泻心汤中、低剂量组比较,半夏泻心汤高剂量组ICCs、ICC-SC数量及nNOS蛋白表达升高,AGEs含量降低(P<0.01)。结论半夏泻心汤能改善DGP模型小鼠的血糖水平、加速胃排空,以高剂量效果最佳,其分子机制可能是抑制胃组织AGEs生成、RAGE表达,促进nNOS表达以调节ICCs及ICC-SC的增殖从而增强DGP小鼠胃动力。
Objective To explore the effects of Banxia Xiexin Decoction(半夏泻心汤)on gastric emptying in diabetic gastroparesis(DGP)mice and the possible mechanism.Methods Thirty female db/db spontaneous type 2 diabetic mice were fed with high-fat and high-sugar diet for one week as adaption,and then DGP mice,when the gastric half emptying time(T1/2)>129 min for two consecutive times,were distinguished with non-DGP mice by 13C caprylic acid breath test.Five non-DGP mice were set as the type 2 diabetes control group,and the DGP mice were randomly divided into the DGP model group,the metoclopramide group,and low-,medium-and high-dose Banxia Xiexin Decoction groups,with five mice in each group.All mice were given 250 mg/(kg·d)of metformin.Additionally,10 mg/(kg·d)of metoclopramide and 750,1500,and 3000 mg/(kg·d)of Banxia Xiexin Decoction were given by gavage to the mice in the metoclopramide group,low-,medium-and high-dose Banxia Xiexin Decoction groups,respectively,all for eight consecutive weeks.After eight weeks,fasting blood glucose was tested,and intraperitoneal glucose tolerance test was performed.The area under the glucose tolerance curve was used to evaluate glucose sensitivity in mice.T1/2 was calculated using the 13C breath test to assess gastric motility.The number of interstitial cells of Cajal(ICCs)and their stem cells(ICC-SC),the content of advanced glycation end products(AGEs),and the expression levels of receptor for advanced glycation endproducts(RAGE)and neuronal nitric oxide synthase(nNOS)in gastric tissue were measured.Results Compared to those in the type 2 diabetes control group,the fasting blood glucose,the glucose area under the curve,and T1/2 of the mice in the DGP model group all increased,while the number of ICCs and ICC-SC in gastric tissue significantly decreased;the content of AGEs and RAGE protein expression increased,while the expression of nNOS protein decreased(P<0.01).Compared to those in the GDP model group and the metoclopramide group,the fasting blood glucose level and the glucose area under the curve of mice in the medium-and high-dose Banxia Xiexin Decoction groups were significantly lower,while the number of ICCs and ICC-SC in gastric tissue significantly increased;the content of AGEs and the expression level of RAGE were significantly lower,while the expression level of nNOS was higher(P<0.01).T1/2 was shortened in the high-dose Banxia Xiexin Decoction group than in the metoclopramide group(P<0.01).The number of ICCs,ICC-SCs and the expression of nNOS protein in the high-dose Banxia Xiexin Decoction group increased,while the content of AGEs decreased compared to those in the medium-and low-dose groups(P<0.01).Conclusion Banxia Xiexin Decoction can improve the level of blood glucose and accelerate gastric emptying in DGP model mice,and the effect is best at high dose.Its molecular mechanism may be related to the inhibition of the production of AGEs and the expression of RAGE,and the up-regulation of the expression of nNOS to regulate the proliferation of ICCs and ICC-SC,thereby enhancing the gastric motility.
作者
李霖芝
丁宁
岳仁宋
LI Linzhi;DING Ning;YUE Rensong(Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,6610075)
出处
《中医杂志》
CSCD
北大核心
2022年第24期2375-2381,共7页
Journal of Traditional Chinese Medicine
基金
国家自然科学资金(81774279)
四川省科技厅重点研发项目(2018SZ0068)
四川省名中医岳仁宋工作室(2100601)
四川省省级科研院所基本科研业务费项目(A-2021N-9)。
关键词
糖尿病胃轻瘫
半夏泻心汤
胃动力
晚期糖基化终末产物
CAJAL间质细胞
diabetic gastroparesis
Banxia Xiexin Decoction(半夏泻心汤)
gastric motility
advanced glycation end products
Cajal interstitial cells
作者简介
通讯作者:岳仁宋,1580229694@qq.com,(028)87780521。
