摘要
目的 探究大豆苷元对肥胖型妊娠期糖尿病孕鼠肝脏脂质代谢的影响及可能作用机制。方法 取60只C57BL/6J雌性小鼠,随机选择其中10只作为正常组,其余小鼠采用高脂高糖饮食、交配后腹腔注射链脲佐菌素方法建立肥胖型妊娠期糖尿病孕鼠模型。将造模成功小鼠随机分为5组,二甲双胍组给予二甲双胍50 mg/(kg·d)灌胃,大豆苷元低、中、高剂量组分别给予25 mg/(kg·d)、50 mg/(kg·d)、100 mg/(kg·d)的大豆苷元灌胃,模型组和正常组给予等量生理盐水灌胃,均1次/d。连续灌胃2周后称量孕鼠体重,测定空腹血糖、胰岛素水平、胰岛素抵抗指数及肝功能指标[谷草转氨酶(AST)、谷丙转氨酶(ALT)]、血脂指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、炎性因子[白细胞介素-1α(IL-1α)、肿瘤坏死因子-α(TNF-α)]、氧化应激指标[超氧化物歧化酶(SOD)、谷胱甘肽(GSH)]水平,HE染色和透射电镜下观察肝组织病理形态及超微结构,Western blot法检测肝脏组织中脂代谢相关蛋白[固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)、过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶-1(CPT-1)、过氧化物酶酰基辅酶A氧化酶1(ACOX1)]表达情况。结果 与正常组比较,模型组孕鼠体重、空腹血糖、胰岛素抵抗指数及血清AST、ALT、TG、TC、LDL-C、IL-1α、TNF-α水平和肝脏组织中SREBP-1c、FAS蛋白相对表达量均明显升高(P均<0.05),血清胰岛素、HDL-C、SOD、GSH水平和肝脏组织中PPARα、CPT-1、ACOX1蛋白相对表达量均明显降低(P均<0.05),肝脏组织出现脂肪空泡和线粒体损伤。与模型组比较,二甲双胍组孕鼠体重、空腹血糖、胰岛素抵抗指数均明显降低(P均<0.05),大豆苷元各剂量组上述各指标变化均不明显(P均>0.05);二甲双胍组和大豆苷元各剂量组孕鼠血清AST、ALT、TG、TC、LDL-C、IL-1α、TNF-α水平和肝脏组织中SREBP-1c、FAS蛋白相对表达量均明显降低(P均<0.05),血清HDL-C、SOD、GSH水平和肝脏组织中PPARα、CPT-1、ACOX1蛋白相对表达量均明显升高(P均<0.05);各药物组肝脏组织脂肪变性和线粒体损伤均明显减轻。结论大豆苷元可改善肥胖型妊娠期糖尿病孕鼠的脂代谢,抑制炎症和氧化应激反应,减轻肝脏脂肪变性和线粒体损伤,机制与调控脂肪酸合成与分解有关。
Objective It is to investigate the effects of daidzein on liver lipid metabolism in obese pregnant rats with gestational diabetes and its potential mechanisms.Methods Sixty female C57BL/6J mice were taken,in which 10 mice were randomly selected as normal group,and the remaining mice were fed with high-fat/high-sugar diet and given streptozotocin by intraperitoneal injection after mating to establish models of obese gestational diabetes.The successfully modeled mice were randomly divided into 5 groups,the metformin group was given metformin 50 mg/(kg·d)by gavage,the low-,medium-,and high-dose groups of daidzein were given daidzein 25 mg/(kg·d),50 mg/(kg·d),and 100 mg/(kg·d)by gavage,respectively,the model group and normal group were given equivalent volumes of physiological saline by gavage,all administered once daily.After 2 weeks of continuous gavage,the pregnant mice were weighed,and the levels of fasting blood glucose,insulin,insulin resistance index,and liver function indicators[aspartate aminotransferase(AST),alanine aminotransferase(ALT)],lipid profiles[total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],inflammatory factors[interleukin-1α(IL-1α),tumor necrosis factor-α(TNF-α)],oxidative stress markers[superoxide dismutase(SOD),glutathione(GSH)]were measured,the histopathological morphology and ultrastructure of liver tissue were observed via HE staining and transmission electron microscopy,and the expressions of lipid metabolism-related proteins in liver tissue[sterol regulatory element-binding protein-1c(SREBP-1c),fatty acid synthase(FAS),peroxisome proliferator-activated receptor alpha(PPARα),carnitine palmitoyl transferase-1(CPT-1)and acyl-CoA oxidase 1(ACOX1)]were detected by Western blot method.Results Compared with the normal group,the body weight,fasting blood glucose,insulin resistance index,and serum levels of AST,ALT,TG,TC,LDL-C,IL-1αand TNF-α,as well as relative protein expressions of SREBP-1c and FAS in liver tissue were all significantly increased in the pregnant mice of model group(all P<0.05),while the serum levels of insulin,HDL-C,SOD and GSH,as well as the relative protein expressions of PPARα,CPT-1 and ACOX1 in liver tissue were all significantly decreased(all P<0.05),fatty vacuoles and mitochondrial damage were observed in liver tissue.Compared with the model group,the body weight,fasting blood glucose and insulin resistance index were all significantly decreased in pregnant mice of the metformin group(all P<0.05),no significant changes in these parameters were observed in each dose group of daidzein(all P>0.05);the serum levels of AST,ALT,TG,TC,LDL-C,IL-1αand TNF-α,as well as relative protein expressions of SREBP-1c and FAS in liver tissue were all significantly decreased in the pregnant mice of metformin group and each dose groups of daidzein(all P<0.05),while the serum levels of insulin,HDL-C,SOD and GSH,as well as the relative protein expressions of PPARα,CPT-1 and ACOX1 in liver tissue were all significantly increased(all P<0.05);the hepatic steatosis and mitochondrial damage were obviously alleviated in all medicated groups.Conclusion Daidzein can improve lipid metabolism,inhibit inflammation and oxidative stress,and alleviate hepatic steatosis and mitochondrial damage in obese pregnant rats with gestational diabetes.The mechanism may be related to regulate fatty acid synthesis and degradation.
作者
华蕾
徐小琼
李春健
邵文璠
李顺序
HUA Lei;XU Xiaoqiong;LI Chunjian;SHAO Wenfan;LI Shunxu(The Third People’s Hospital of Yunnan Province,Kunming 650011,Yunnan,China)
出处
《现代中西医结合杂志》
2025年第14期1911-1917,1992,共8页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
云南省科技计划重点项目(202101BA070001-223)。
