摘要
目的观察糖复康方对自发性糖尿病(KKAy)小鼠的治疗作用及机制。方法选取KKAy小鼠36只及C57BL/6J野生型小鼠6只,C57BL/6J小鼠作为正常组给予正常饮食,KKAy小鼠给予高脂饮食。将36只KKAy小鼠采用随机数字表法分为模型组、中药组、中药+抑制剂组、激动剂组,各9只。中药组、中药+抑制剂组给予3.2 g/(kg·d)糖复康方灌胃,正常组、模型组、激动剂组给予等量生理盐水灌胃,1次/d,共4周。激动剂组给予0.5 g/(kg·d)5-氨基咪唑-4-甲酰胺核糖核苷(AICAR)腹腔注射,中药+抑制剂组给予5 mg/(kg·d)剂量的化合物c(CC)腹腔注射,正常组、模型组、中药组给予等量磷酸盐缓冲液腹腔注射,1次/d,共4周。比较各组随机血糖(RBG),口服葡萄糖耐量试验(OGTT)结果,血浆脂联素(APN)、支链氨基酸(BCAA),骨骼肌中腺苷5-单磷酸激活蛋白激酶(AMPK)α、p-AMPKα、支链α-酮酸脱氢酶(BCKDH)-E1α、p-BCKDH-E1α蛋白表达水平,骨骼肌、胰腺组织病理变化及安全性指标。结果干预第2周,与中药+抑制剂组比较,中药组、激动剂组RBG水平低(P<0.01);中药组与激动剂组RBG比较,差异无统计学意义(P>0.05)。干预4周后,中药组、激动剂组RBG均较治疗前降低(P<0.01)。干预后各观察时点,中药组、激动剂组RBG水平均低于模型组(P<0.01)。干预4周后,模型组血浆APN低于正常组,BCAA水平高于正常组(P<0.05);与模型组比较,中药组、激动剂组血浆APN水平高,BCAA水平低(P<0.01);中药+抑制剂组血浆APN、BCAA水平较模型组差异无统计学意义(P>0.05)。与模型组比较,中药组、激动剂组骨骼肌细胞排列整齐、规则,肌细胞水肿、萎缩和断裂明显减轻,炎症细胞有所减少,骨骼肌组织中p-AMPKα/AMPKα、p-BCKDH-E1α/BCKDHE1α水平高(P<0.05)。与模型组比较,中药组、激动剂组谷丙转氨酶(ALT)均低(P<0.01),中药+抑制剂组差异无统计学意义(P>0.05)。与模型组比较,中药组谷草转氨酶(AST)、尿素(Urea)、肌酐(Crea)均低(P<0.05),激动剂组、中药+抑制剂组差异均无统计学意义(P>0.05)。结论糖复康方可改善KKAy糖尿病小鼠糖脂代谢,且安全性高,其作用机制可能与APNAMPK-BCAA信号通路有关。
Objective To observe the therapeutic effect and mechanism of the Tangfukang Formula on spontaneous diabetes(KKAy)mice.Methods Thirty-six KKAy mice and six C57BL/6J wild-type mice were selected,with C57BL/6J mice serving as the normal group and receiving a normal diet,while KKAy mice were given a high-fat diet.The 36 KKAy mice were randomly divided into model group,Chinese medicine group,Chinese medicine+inhibitor group,and agonist group according to a random number table,with 9 mice in each group.The Chinese medicine group and Chinese medicine+inhibitor group were administered 3.2 g(/kg·d)of Tangfukang Formula by gavage.The normal,model,and agonist groups received an equivalent volume of physiological saline by gavage,once per day for 4 weeks.The agonist group was injected intraperitoneally with 0.5 g(/kg·d)5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),and the Chinese medicine+inhibitor group was injected with 5 mg(/kg·d)compound C(CC)intraperitoneally.The normal,model,and Chinese medicine groups received an equivalent volume of phosphate buffer solution by intraperitoneal injection,once per day for 4 weeks.Random blood glucose(RBG),oral glucose tolerance test(OGTT),plasma adiponectin(APN)and branched-chain amino acids(BCAA),protein expression levels of AMPKα,p-AMPKα,BCKDH-E1α,and p-BCKDH-E1αin skeletal muscle,as well as histopathological changes in skeletal muscle and pancreatic tissues,were assessed.Safety indicators were also measured.Result After 2 weeks of intervention,RBG levels in the Chinese medicine group and agonist group were lower than those in the Chinese medicine+inhibitor group(P<0.01),with no significant difference between the Chinese medicine and agonist groups(P>0.05).After 4 weeks,RBG levels in the Chinese medicine and agonist groups were significantly reduced compared to those before treatment(P<0.01),and their RBG levels were lower than those of the model group at all observed time points(P<0.01).After 4 weeks,plasma APN levels in the model group were lower than in the normal group,while BCAA levels were higher(P<0.05).Compared with the model group,both the Chinese medicine and agonist groups had higher APN levels and lower BCAA levels(P<0.01).There was no significant difference in APN and BCAA levels between the Chinese medicine+inhibitor group and the model group(P>0.05).Histopathological examination showed that in the Chinese medicine and agonist groups,skeletal muscle cells were more orderly with less edema,atrophy,and rupture of muscle fibers,and fewer inflammatory cells.In these groups,the levels of p-AMPKα/AMPKαand p-BCKDH-E1α/BCKDH-E1αin skeletal muscle tissue were significantly higher(P<0.05).Compared with the model group,the Chinese medicine and agonist groups showed significantly lower alanine aminotransferase(ALT)levels(P<0.01),while there was no significant difference in the Chinese medicine+inhibitor group(P>0.05).The Chinese medicine group also showed significantly lower aspartate aminotransferase(AST),urea,and creatinine(Crea)levels compared to the model group(P<0.05),while no significant differences were observed in the agonist and Chinese medicine+inhibitor groups(P>0.05).Conclusion Tangfukang Formula has a clear effect on improving the metabolism of glucose and lipid in KKAy diabetes mice,and has good safety.Its mechanism may be related to APN-AMPK-BCAA signaling pathway.
作者
闫凯
王燕
王威
李建辉
冯兴中
YAN Kai;WANG Yan;WANG Wei;LI Jianhui;FENG Xingzhong(Department of Traditional Chinese Medicine,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100043,China;Department of Traditional Chinese Medicine,Civil Aviation General Hospital,Beijing 100123;Endocrinology Department,Yuquan Hospital of Tsinghua University(Tsinghua University Integrated Traditional Chinese and Western Medicine Hospital),Beijing 100040)
出处
《北京中医药》
2025年第2期142-148,共7页
Beijing Journal of Traditional Chinese Medicine
基金
首都卫生发展科研专项(首发2022-2-4131)
北京市中医药科技发展资金项目(BJZYZD-2023-01)。
