糖肝煎对2型糖尿病大鼠摄食...食抑制因子1、饥饿素的影响_陶毅.pdf

安 徽 医 药 Anhui Medical and Pharmaceutical Journal 2023 Feb，27（2）糖肝煎对2型糖尿病大鼠摄食及摄食抑制因子1、饥饿素的影响陶毅，徐乃佳，胡爱民作者单位：武汉市中医医院内分泌科，湖北 武汉430000通信作者：胡爱民，男，主任医师，研究方向为糖尿病的中西医治疗，Email：基金项目：武汉市卫生和计划生育委员会科研项目（WZ18D14）摘要：目的 探究糖肝煎对2型糖尿病（T2DM）大鼠摄食及血浆摄食抑制因子1（Nesfatin-1）、饥饿素（Ghrelin）的影响。方法 将50只SD大鼠采用随机数字表法分成正常组、T2DM组、利格列汀组（50 mg/kg利格列汀）、低剂量组（2.8 g/kg糖肝煎）、高剂量组（5.6 g/kg糖肝煎），10只/组；通过尾静脉注射链脲佐菌素（STZ）及高脂饲料进行T2DM大鼠模型构建；利格列汀组、低剂量组及高剂量组连续4周给予相应药物灌胃，正常组及T2DM组给予等量生理盐水，1次/天，于实验结束后观察大鼠一般情况，并称取大鼠体质量，测定摄食量、摄水量、尿量；全自动生化分析仪测定大鼠血清空腹血糖（FBG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、三酰甘油（TG）及总胆固醇（TC）水平；计算大鼠口服葡萄糖耐量试验（OGTT）曲线下面积（AUC）；酶联免疫吸附试验（ELISA）检测血清胰岛素（INS）水平及血浆核连蛋白2（NUCB2）、Ghrelin、Nesfatin-1水平；实时荧光定量逆转录聚合酶链式反应（qRT-PCR）检测血浆Nesfatin-1、Ghrelin mRNA水平。结果 正常组大鼠粪便正常，皮毛光泽顺滑，行动灵活、精神状态良好；T2DM组大鼠出现便溏，精神不振、皮毛发黄粗糙；相较于T2DM组，利格列汀组、低剂量组、高剂量组大鼠上述症状存在不同程度改善；相较于正常组，T2DM组大鼠血清FBG水平、OGTT AUC、摄食量、摄水量、尿量、LDL-C、TG、TC、Ghrelin水平显著增加，INS水平、体质量、HDL-C、NUCB2、Nesfatin-1水平显著降低（P0.05）；相较于T2DM组，利格列汀组、低剂量组、高剂量组FBG水平、OGTT AUC、摄食量、摄水量、尿量、LDL-C、TG、TC、Ghrelin水平显著降低，INS水平、体质量、HDL-C、NUCB2、Nesfatin-1水平显著增加（P0.05）；相较于低剂量组，高剂量组血清FBG水平、OGTT曲线下区域面积、摄食量、摄水量、尿量、LDL-C、TG、TC、Ghrelin水平显著降低，INS水平、体质量、HDL-C、NUCB2、Nesfatin-1水平显著增加（P0.05）。结论 糖肝煎可抑制T2DM大鼠摄食，增加其体质量及血浆Nesfatin-1水平，降低Ghrelin水平。关键词：糖尿病，2型；摄食；人摄食抑制因子1；饥饿素；糖肝煎Effect of Tanggan decoction on food intake,Nesfatin-1 and Ghrelin in type 2 diabetic ratsTAO Yi,XU Naijia,HU AiminAuthor Affiliation:Department of Endocrinology,Wuhan Hospital of Traditional Chinese Medicine,Wuhan,Hubei 430000,ChinaAbstract：Objective To explore the effect of Tanggan decoction on food intake and plasma NUCB2-encoded satiety and fat-influencing protein 1(Nesfatin-1)and ghrelin in in rats with type 2 diabetes mellitus(T2DM).Methods Fifty SpragueDawley(SD)rats were divided into a normal group,T2DM group,linagliptin group(50 mg/kg linagliptin),low-dose group(2.8 g/kg Tanggan decoction),and high-dose group(5.6 g/kg Tanggan decoction),with 10 rats per group.The T2DM rat model was established by tail vein injection of streptozotocin(STZ)and a high-fat diet;Rats in the ligliptin,low-dose and high-dose groups were given the corresponding drugs by gavage for 4 consecutive weeks,and the normal and T2DM groups were given equal amounts of saline once/day.After the experiment,the general condition of the rats was observed,the body mass of the rats was determined,and the amount of food intake,water intake and urine output were measured.Serum fasting blood glucose(FBG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG)and total cholesterol(TC)levels were determined by an automatic biochemical analyzer;the area under the curve(AUC)of the oral glucose tolerance test(OGTT)in rats was calculated;serum insulin(INS)levels and plasma nucleonectin 2(NUCB2),ghrelin,nesfatin-1 levels were measured by enzyme-linked immunosorbent assay(ELISA);and plasma levels of nesfatin-1 and ghrelin mRNA were detected with real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRTPCR).Results The rats in the normal group had normal stools,smooth and shiny fur,flexible movement and good mental status;while the rats in the T2DM group had loose stools,poor mental health,and yellow and rough fur.Compared with the T2DM group,the rats in the linagliptin,low-dose,and high-dose groups had different degrees of improvement in the above symptoms.Compared with the normal 药学研究引用本文：陶毅，徐乃佳，胡爱民.糖肝煎对2型糖尿病大鼠摄食及摄食抑制因子1、饥饿素的影响 J.安徽医药，2023，27（2）：246-250.DOI：10.3969/j.issn.1009-6469.2023.02.008.246安 徽 医 药 Anhui Medical and Pharmaceutical Journal 2023 Feb，27（2）group,the rats in the T2DM group had significantly higher serum FBG levels,OGTT AUC,food intake,water intake,urine output,LDL-C,TG,TC and ghrelin levels,and significantly lower INS levels,body weight,HDL-C,NUCB2 and nesfatin-1 levels(P 0.05).Compared with the T2DM group,the rats in the linagliptin,low-dose and high-dose groups showed significantly lower FBG levels,OGTT AUC,food intake,water intake,urine output,LDL-C,TG,TC and Ghrelin levels,and significantly higher INS levels,body weight,HDL-C,NUCB2,and nesfatin-1 levels(P0.05).Compared with the low-dose group,serum FBG levels,OGTT AUC,food intake,water intake,urine output,LDL-C,TG,TC,and ghrelin levels were significantly lower,and INS levels,body weight,HDL-C,NUCB2,and nesfatin-1 levels were significantly higher in the high-dose group(P0.05).Conclusion Tanggan decoction can inhibit food intake,increase body weight and plasma nesfatin-1 levels,and decrease ghrelin levels in T2DM rats.Key words：Diabetes mellitus,type 2;Food intake;Nesfatin-1;Ghrelin;Tanggan decoction2 型糖尿病（type 2 diabetes mellitus，T2DM）是一种以胰岛细胞损伤及胰岛素抵抗（insulin resistance，IR）为临床特征的代谢性疾病1。T2DM慢性高血糖会对机体脏器产生长期损害，从而严重影响患者的生活质量2。研究发现，摄食过盛造成的能量代谢紊乱与糖尿病的发生密切相关，摄食抑制因子 1（Nesfatin-1）是一种由核连蛋白 2（nucleobindin 2，NUCB2）水解产生的摄食抑制因子，而最近研究表明，其还具有抗高血糖的作用3。饥饿素（Ghrelin）作为生长激素释放肽不仅可通过激活机体下丘脑神经回路来刺激食物的摄取，其缺失还可降低血糖并促使胰岛素（insulin，INS）分泌4。Nesfatin-1与Ghrelin作为机体能量代谢的调控因子，可通过调控食物摄取能力来改变摄食量，从而调控机体的能量代谢，已得到多项研究证实，但关于中草药在