摘要
目的观察桃红四物汤对糖尿病脑病(diabetic encephalopathy,DE)模型大鼠脑神经细胞的保护作用及机制。方法采用高糖、高脂饲料喂养以及链脲佐菌素诱导复制DE模型大鼠。选取成功建立的DE模型大鼠,随机分为模型组(蒸馏水),桃红四物汤低剂量(4.5 g/kg,相当于临床等效剂量1倍)、中剂量(9 g/kg)、高剂量(18 g/kg)组,二甲双胍组(0.2 g/kg),多奈哌齐组(1 mg/kg),每组10只,另取正常雄性大鼠10只作为对照组,每天灌胃给药1次,连续5周。观察各组大鼠血糖与体质量的变化,采用Morris水迷宫实验观察各组大鼠学习和空间记忆能力,采用试剂盒检测各组大鼠血清三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和脑组织过氧化脂质(lipid peroxide,LPO)含量和一氧化氮合酶(nitric oxide synthase,NOS)的活性,苏木精-伊红染色观察各组大鼠海马组织神经细胞形态学变化,实时定量聚合酶链反应检测各组大鼠脑组织淀粉样前体蛋白(amyloid precursor protein,APP)、β-分泌酶(β-secretase,BACE1)、β-淀粉样蛋白(amyloid-β,Aβ)mRNA表达水平。结果桃红四物汤能显著降低DE模型大鼠血糖水平(P<0.05),显著改善DE模型大鼠的学习记忆能力(P<0.05),能显著降低DE模型大鼠体内TG、TC、LDL-C水平(P<0.05),升高体内HDL-C水平(P<0.05),能显著减少DE模型大鼠海马组织神经细胞的损伤,降低脑组织内LPO含量、NOS活性(P<0.05),能显著抑制DE模型大鼠海马组织中APP、BACE1、Aβ_(1-40)、Aβ_(1-42)的表达水平(P<0.05)。结论桃红四物汤能够降低DE模型大鼠脑内氧化应激反应,通过抑制APP和BACE1的表达,减少Aβ的积聚,发挥神经细胞保护作用,改善DE模型大鼠的学习记忆能力。
Objective To investigate the protective effect and mechanism of Taohong Siwu Decoction(THSWD)on brain neural cells in a rat model of diabetic encephalopathy(DE).Methods A rat model of DE was established by high-glucose high-fat diet and streptozotocin.After successful modeling,DE model rats were randomly divided into model group(distilled water),low-dose THSWD group(4.5 g/kg,equal to 1 time of clinical equivalent dose),middle-dose THSWD group(9 g/kg),high-dose THSWD group(18 g/kg),metformin positive drug group(0.2 g/kg),and donepezil positive drug group(1 mg/kg),with 10 rats in each group,and 10 normal male rats were selected as control group;the rats were administered by gavage once a day for 5 consecutive weeks.The changes in blood glucose and body weight were observed for the rats in each group;Morris water maze test was used to observe learning and spatial memory abilities;related kits were used to measure the serum levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)and the content of LPO and the activity of NOS in brain tissue;HE staining was used to observe the changes in the morphology of neural cells in the rat hippocampus;quantitative real-time PCR was used to measure the mRNA expression levels of amyloid precursor protein(APP),β-secretase(BACE1),andβ-amyloid(Aβ)in brain tissue.Results In the rats with DE,THSWD significantly reduced the level of blood glucose(P<0.05),significantly improved learning and memory abilities(P<0.05),and significantly reduced the levels of the blood lipids TG,TC,LDL-C,and HDL-C(P<0.05),the damage of neural cells in the rat hippocampus(P<0.05),and the content of LPO and the activity of NOS in brain tissue(P<0.05).It also significantly inhibited the expression of APP,BACE1,Aβ_(1-40),and Aβ_(1-42) in the hippocampus(P<0.05).Conclusion THSWD can reduce oxidative stress response in the brain of rats with DE,and it exerts a protective effect on neural cells and improves the learning and memory abilities of DE model rats by inhibiting the expression of APP and BACE1 and reducing the accumulation of Aβ.
作者
章梦玲
蔡明
夏文文
戴文涛
赵梦蝶
韩燕全
韩岚
彭代银
ZHANG Meng-ling;CAI Ming;XIA Wen-wen;DAI Wen-tao;ZHAO Meng-die;HAN Yan-quan;HAN Lan;PENG Dai-yin(Anhui University of Chinese Medicine, Anhui Hefei 230012, China;Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Hefei 230012, China;Key Laboratory of Chinese Medicinal Formula Research, Anhui Hefei 230012, China;The Second Affiliated Hospital of Anhui University of Chinese Medicine, Anhui Hefei 230061, China;Lu'an Hospital of Traditional Chinese Medicine, Anhui Lu'an 237000, China;The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui Hefei 230031, China)
出处
《安徽中医药大学学报》
CAS
2022年第3期64-70,共7页
Journal of Anhui University of Chinese Medicine
基金
国家自然科学基金项目(82074152)
安徽中医药大学临床科研项目(2021efylc03)。
关键词
桃红四物汤
糖尿病脑病
神经细胞
认知功能障碍
Taohong Siwu Decoction
Diabetic encephalopathy
Neural cell
Cognitive disorder