机构地区:[1]安徽中医药大学中医学院,安徽省合肥市230012 [2]安徽中医药大学第一附属医院
出 处:《中医杂志》2025年第2期178-187,共10页Journal of Traditional Chinese Medicine
基 金:国家自然科学基金(82174153,82474431);安徽省高校协同创新项目(GXXT-2020-025);合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所“揭榜挂帅”项目(2023CXMMTCM003)。
摘 要:目的 探讨半夏泻心汤治疗糖尿病性胃轻瘫(DGP)的可能作用机制。方法 29只SD大鼠随机分为空白组5只及模型组、半夏泻心汤组和二甲双胍组各8只。除空白组外,余下各组采用腹腔注射1%链脲佐菌素(STZ)溶液结合高糖高脂饲料不规则喂养制备DGP大鼠模型。造模成功后半夏泻心汤组予半夏泻心汤6.68 g/(kg·d)灌胃,二甲双胍组予盐酸二甲双胍105 mg/(kg·d)灌胃,空白组与模型组予生理盐水6.68 ml/(kg·d)灌胃,连续8周。末次给药后检测大鼠空腹血糖(FBG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG);计算胃排空率;ELISA法检测胃组织中胃肠激素胃动素(MTL)、胃泌素(GAS)及炎症因子肿瘤坏死因子(TNF-α)、白细胞介素6 (IL-6)、白细胞介素1β (IL-1β)和白细胞介素10 (IL-10)水平;油红O观察大鼠肝脏病理形态,HE染色观察胃窦组织病理形态;免疫荧光法检测大鼠肝脏中肝X受体α (LXRα)水平;Western Blot法检测肝脏组织LXRα和胃窦组织非受体型酪氨酸蛋白激酶2 (JAK2)、磷酸化非受体型酪氨酸蛋白激酶2 (p-JAK2)、信号转导及转录激活蛋白3 (STAT3)与磷酸化信号转导及转录激活蛋白3 (p-STAT3)水平,qPCR法检测肝脏组织LXRα和胃窦组织JAK2、STAT3 mRNA表达。结果 与空白组比较,模型组大鼠肝脏出现明显的脂肪变性,胃窦组织结构被破坏;FBG、HbA1c、TC、TG水平升高;肝脏组织LXRα平均荧光强度、蛋白水平及相应mRNA表达均降低;胃排空率及胃组织GAS、MTL、IL-10含量下降,胃组织TNF-α、IL-6、IL-1β含量升高;胃窦组织p-JAK2/JAK2与p-STAT3/STAT3和JAK2、STAT3mRNA表达上升(P<0.01)。与模型组比较,半夏泻心汤组及二甲双胍组肝脏与胃窦组织的病理形态改善;FBG、HbA1c、TC、TG水平降低;肝脏组织LXRα平均荧光强度、蛋白水平及相应mRNA表达升高;胃排空率及胃组织GAS、MTL、IL-10含量升高,TNF-α、IL-6、IL-1β含量下降;胃窦组织p-JAK2/JAK2、p-STObjective To explore the potential mechanism of Banxia Xiexin Decoction(半夏泻心汤,BXD)in the treatment of diabetic gastroparesis(DGP).Methods A total of 29 SD rats were randomly divided into four groups,blank group(5 rats)and model group,BXD group and metformin group(8 rats in each group).Except for the blank group,rats were administered intraperitoneally with 1%streptozotocin(STZ)solution and were fed a high-sugar,high-fat diet to establish the DGP rat model.After successful modeling,the BXD group was treated with BXD at 6.68 g/(kg·d)by gavage,the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d)by gavage,and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d)by gavage,for 8 weeks.After the last administration,fasting blood glucose(FBG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglycerides(TG)were measured and gastric emptying rate was calculated.ELISA was used to detect the levels of gastrointestinal hormones motilin(MTL)and gastrin(GAS),as well as inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and interleukin-10(IL-10)in gastric tissue.Oil red O staining was performed to observe liver pathological morphology.Hematoxylin and eosin(HE)staining was used to observe gastric antrum tissue morphology.Immunofluorescence staining was used to detect liver X receptorα(LXRα)levels in the liver.Western Blot was used to detect the protein levels of LXRαin liver tissue,and of janus kinase 2(JAK2),phospho-janus kinase 2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phospho-signal transducer and activator of transcription 3(p-STAT3)in gastric antrum tissue.Quantitative real-time polymerase chain reaction(qPCR)was used to measure the mRNA expression of LXRαin liver tissue and JAK2,STAT3 in gastric antrum tissue.Results Compared with the blank group,the model group showed significant hepatic fatty degeneration,gastric antrum tissue structure destruction,and increases i
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