摘要
目的探讨葫芦巴碱(trigonelline,TRG)对妊娠期糖尿病(gestational diabetes mellitus,GDM)大鼠血脂代谢及胰岛素抵抗的影响。方法随机选取8只雌性Wistar大鼠普通喂养,剩余大鼠高脂喂养8周,均合笼交配确认妊娠后,取普通喂养大鼠作为对照组,高脂喂养大鼠腹腔注射小剂量链脲佐菌素(streptozotocin,STZ)35 mg/kg诱导构建GDM模型,成模大鼠随机分为模型组、TRG低剂量组(15 mg/(kg·d))、TRG高剂量组(45 mg/(kg·d))及盐酸二甲双胍(MH)(200 mg/(kg·d))组,每组各8只,对照组及模型组大鼠仅灌胃给药等量生理盐水,连续14 d。称重并测量大鼠空腹血糖(fasting blood glucos,FBG)水平及24 h尿白蛋白(albumin,Alb)含量;收集血液,检测血脂(高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三酯(TG))、肝功能(天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT))及肾功能(血尿素氮(blood urea nitrogen,BUN)、肌酐(serum creatinine,SCr));检测各组大鼠空腹胰岛素(fasting insulin,FINS)含量;计算胰岛素抵抗指数(HOMA-insulin resistance index,HOMA-IR)及胰岛素敏感指数(HOMA-insulin sensitivity index,HOMA-ISI);观察大鼠胰腺组织病理学变化;检测胰腺组织中超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、丙二醛(malondialdehyde,MDA)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及白细胞介素6(interleukin 6,IL-6)水平。结果成功构建GDM大鼠模型;与对照组比较,模型组、TRG低、高剂量组及MH组大鼠BM、24 h Alb、AST、ALT、BUN及SCr、FBG水平、血清LDL-C、TC和TG含量、FINS、HOMA-IRI值、胰腺组织中MDA、TNF-α和IL-6水平升高,血清HDL-C含量、HOMA-ISI值及胰腺组织中SOD、CAT活性水平降低(P<0.05),胰腺组织见有不同程度的病理变化;与模型组比较,TRG低、高剂量组及MH组大鼠BM、24 h Alb、AST、ALT、BUN及SCr、FBG水平、血清LDL-C、TC和TG含量、FINS、HOMA-IRI值、胰腺组织中MDA、TNF-α和IL-6水平降低,血清HDL-C含量、HOMAISI值及胰腺组织中SOD、CAT活性水平升高(P<0.05),胰腺组织病理损伤逐渐减轻;TRG低、高剂量组及MH组作用效果逐渐增强(P<0.05)。结论TRG可降低GDM大鼠血糖水平,改善肝肾功能及异常血脂代谢,减轻胰岛素抵抗并提高胰岛素敏感性,其作用效果可能与降低炎性及氧化水平有关。
Objective To investigate the effects of trigonelline(TRG)on lipid metabolism and insulin resistance in gestational diabetes mellitus(GDM)rats.Methods Eight female Wistar rats were randomly selected for normal feeding,and the remaining rats were fed a high fat diet for 8 weeks.After cage mating to confirm pregnancy,normal fed rats were used as the control group,and the high fat fed rats were intraperitoneally injected with 35 mg/kg streptozotocin to induce the GDM model.Model rats were randomly divided into model,TRG low-dose(15 mg/(kg·d)),TRG high-dose(45 mg/(kg·d))and metformin hydrochloride(MH)(200 mg/(kg·d))groups with eight rats in each group.Control and model groups were treated with the same amount of normal saline by intragastric administration for 14 consecutive days.Weigh and the fasting blood glucose(FBG)were measured.BM and the contents of 24 h Alb,AST,ALT,BUN,and SCr,serum high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),and triglyceride(TG)were measured.Fasting insulin(FINS)content was measured in each group.Insulin resistance index(HOMA-IR)and insulin sensitivity index(HOMA-ISI)were calculated.Histopathological changes of the pancreas in rats were observed.Levels of superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),and interleukin 6(IL-6)in pancreatic tissues were measured.Results The GDM rat model was successfully established.Compared with the findings in the control group,FBG,serum LDL-C,TC and TG,FINS,HOMA-IRI,MDA,and TNF-αand IL-6 levels in pancreatic tissue were increased,serum HDL-C content,HOMAISI,and SOD and CAT activities in pancreatic tissue were decreased in model,TRG low-dose,TRG high-dose,and MH groups(P<0.05),and pathological changes of various degrees were found in pancreatic tissue.Compared with the findings in the model group,in TRG low-dose,TRG high-dose,and MH groups,FBG,serum LDL-C,TC and TG,FINS,HOMAIRI,MDA,and TNF-αand IL-6 levels in pancreatic tissue were decreased,serum HDL-C content,HOMA-ISI,and SOD and CAT activities in pancreatic tissue were increased(P<0.05),and pathological injury of pancreatic tissue was gradually decreased.The effect of TRG in low-dose,high-dose,and MH groups was gradually enhanced(P<0.05).Conclusions Trigonelline reduces the blood glucose level,improves liver and kidney functions,and abnormal blood lipid metabolism,reduces insulin resistance and improves insulin sensitivity in GDM rats.Its effect may be related to reducing inflammation and oxidization.
作者
张艳红
王柯静
李丽娟
李果
ZHANG Yanhong;WANG Kejing;LI Lijuan;LI Guo(Department of Obstetrics and Gynecology,Zhengzhou Institute of Industrial Application Technology,Xinzheng 451100,China.;Department of Obstetrics and Gynecology,Xinzheng Public People’s Hospital,Xinzheng 451150)
出处
《中国比较医学杂志》
CAS
北大核心
2023年第8期68-74,共7页
Chinese Journal of Comparative Medicine
基金
河南省2020年科技发展计划(202102310067)。
