香砂六君子汤对脾虚高脂血症大鼠肝脏内质网应激/PERK/SREBP1c途径及甘油三酯合成的影响及机制  

The Effect and Mechanism of Xiangsha Liujunzi Decoction on Liver Endoplasmic Reticulum Stress/PERK/SREBP1c Pathway and TG Synthesis in Spleen Deficiency Hyperlipidemia Rats

作　　者：张琦[1] 隋国媛 宋囡[1] 王杰[1] 黄艳阳 贾连群[1] ZHANG Qi;SUI Guo-yuan;SONG Nan;WANG Jie;HUANG Yan-yang;JIA Lian-qun(Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110847,China)

机构地区：[1]辽宁中医药大学,辽宁汉沈阳110847

出　　处：《时珍国医国药》2024年第3期545-550,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81974548,82074145,82374423);辽宁省高校黄大年式教师团队项目。

摘　　要：目的 探讨香砂六君子汤对脾虚高脂血症大鼠肝脏内质网应激/PERK/SREBP1c途径及甘油三酯合成的影响及机制。方法 将24只SPF级SD大鼠随机分为空白对照组、高脂模型组、脾虚高脂组以及香砂六君子汤组,每组6只。脾虚高脂组以及香砂六君子汤组采用饮食不节加力竭游泳方法建立脾虚模型。除空白对照组外,其余各组给予高脂饲料喂养,于第10周开始灌胃,香砂六君子汤组给予香砂六君子汤11.34g/(kg·d),其余各组给予等体积的生理盐水灌胃,4周后取材。全自动生化分析仪检测血脂水平;HE染色观察肝脏病理变化;油红O染色观察肝脏脂质沉积情况;微板法检测肝脏组织TG水平;RT-qPCR法检测肝脏组织GRP78、SREBP-1c、ACC1 mRNA表达水平,Western blotting法检测肝脏组织PERK、p-PERK、GRP78、SREBP-1c、ACC1蛋白表达水平。结果 与空白对照组比较,高脂模型组以及脾虚高脂组大鼠血清TC、TG、LDL-C水平显著升高,HDL-C水平显著降低(P<0.05或P<0.01);肝细胞中细胞质疏松呈网状,脂肪空泡明显,橘色脂滴显著,弥漫性分布;肝脏组织中TG水平显著升高(P<0.01),GRP78、SREBP-1c、ACC1 mRNA及蛋白表达显著升高(P<0.05或P<0.01),p-PERK蛋白相对表达水平显著升高(P<0.05)。与高脂模型组比较,脾虚高脂组大鼠血清TC水平显著升高,HDL-C水平显著降低(P<0.05),TG、LDL-C水平有升高趋势;肝脏组织中TG水平显著升高(P<0.01),GRP78、SREBP-1c、ACC1 mRNA及蛋白表达显著升高(P<0.05或P<0.01),p-PERK蛋白表达水平显著升高(P<0.05)。与脾虚高脂组比较,香砂六君子汤组大鼠血清TC、TG、LDL-C水平显著降低,HDL-C水平显著升高(P<0.01);肝细胞细胞质疏松程度减轻,脂肪空泡和橘色脂滴显著减少;肝脏组织中TG水平显著降低(P<0.01),GRP78、SREBP-1c、ACC1 mRNA及蛋白表达显著降低(P<0.01),p-PERK蛋白表达水平显著降低(P<0.01)。结论 香砂六君子汤可能通过调控内质网应激/PERK/SREBP1Objective To explore the effect and mechanism of Xiangsha Liujunzi Decoction on liver endoplasmic reticulum stress/PERK/SREBP1c pathway and TG synthesis in spleen deficiency hyperlipidemia rats. Methods 24 SPF SD rats were randomly divided into blank control group, hyperlipidemia model group, spleen deficiency hyperlipidemia group and Xiangsha Liujunzi decoction group with 6 rats in each group. The spleen deficiency model was established by diet and exhaustive swimming in the spleen deficiency high fat group and Xiangsha Liujunzi decoction group. Except for the blank control group, the other groups were fed with high-fat diet and began to be gavaged at the 10th week. The Xiangsha Liujunzi decoction group was given 11.34g/(kg ·d), and the other groups were given the same volume of normal saline for 4 weeks. The level of blood lipid was detected by automatic biochemical analyzer, the pathological changes of liver were observed by HE staining, the lipid deposition of liver was observed by oil red O staining, the level of TG in liver tissue was detected by microplate method, the expression level of GRP78, SREBP-1c and ACC1mRNA in liver tissue was detected by RT-qPCR method, and the expression level of PERK, p-PERK, GRP78, SREBP-1c and ACC1 protein in liver tissue was detected by Western blotting method. Results Compared with the blank control group, the serum levels of TC, TG and LDL-C in the hyperlipidemia model group and spleen deficiency hyperlipidemia group increased significantly, while the level of HDL-C decreased significantly(P < 0.05or P< 0.0l), and the cytoplasmic porosity in hepatocytes was reticular, fat vacuoles were obvious, orange lipid droplets were obvious and diffuse distribution. The level of TG(P< 0.0l), GRP78, SREBP-1c, ACC1mRNA and protein expression in liver tissue were significantly increased(P< 0.05or P< 0.0l), and the relative expression level of p-PERK protein was significantly increased(P< 0.05). Compared with the hyperlipidemia model group, the level of serum TC in the spleen deficiency

关 键 词：内质网应激 血脂异常 香砂六君子汤 脾虚 

分 类 号：R285.5[医药卫生—中药学]