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补阳还五汤对高脂血症模型金黄地鼠血脂水平及SREBP-2/Pcsk9信号通路的影响 被引量:11

Effects of Buyang Huanwu Decoction on the Lipid Level and SREBP-2/Pcsk9 Signaling in Hyperlipemia Golden Hamster(Mesocricetus auratus)
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摘要 目的研究补阳还五汤对高脂血症模型金黄地鼠血脂水平及胆固醇调节元件结合蛋白2型(SREBP-2)/前蛋白转化酶枯草杆菌蛋白酶9型(Pcsk9)信号通路的影响。方法 60只金黄地鼠采用随机数字表法随机分为正常组、模型组、补阳还五汤低、中、高(5、10、20g/kg)剂量组和辛伐他丁(0.01g/kg)组,每组10只。正常组地鼠给予普通饲料,其余组地鼠给予高脂饲料建立高脂血症模型,4周后同时灌胃给予相应药物,正常组和模型组地鼠灌胃给予等体积蒸馏水,每天1次,连续给药4周。末次给药后,检测各组地鼠血总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDL-C)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT),肝脏组织病理及油红O染色,肝脏组织SREBP-2、Pcsk9、低密度脂蛋白受体(LDL-R)蛋白表达水平。结果与正常组比较,模型组地鼠血TC、TG、LDL-C、AST、ALT水平增高[TC:(20.64±4.98)mmol/L比(1.31±0.23)mmol/L,TG:(19.20±6.88)mmol/L比(0.65±0.01)mmol/L,LDL-C:(17.91±2.69)mmol/L比(1.35±0.28)mmol/L,AST:(193.47±28.53)U/L比(25.37±5.58)U/L,ALT:(146.57±37.10)U/L比(47.43±14.52)U/L,P均<0.01],HDL-C水平降低[(1.06±0.48)mmol/L比(3.64±0.74)mmol/L,P<0.01];SREBP2、Pcsk9、LDL-R蛋白表达降低(P<0.05或P<0.01);肝脏组织脂肪浸润明显,脂肪空泡明显增加,脂质沉积。与模型组比较,补阳还五汤中、高剂量组地鼠血TC、TG、LDL-C、AST、ALT水平降低[TC:(16.07±2.68)mmol/L、(8.58±3.57)mmol/L比(20.64±4.98)mmol/L,TG:(12.42±3.60)mmol/L、(9.83±2.60)mmol/L比(19.20±6.88)mmol/L,LDL-C:(10.16±3.14)mmol/L、(13.86±2.56)mmol/L比(17.91±2.69)mmol/L,AST:(134.13±51.15)U/L、(107.21±56.32)U/L比(193.47±28.53)U/L,ALT:(130.55±47.49)U/L、(92.01±33.52)U/L比(146.57±37.10)U/L,P<0.05或P<0.01],HDL-C水平升高[(1.71±0.44)mmol/L、(2.26±0.52)mmol/L比(1.06±0.48)mmol/L,P<0.05或P<0.01],SREBP2、Pcsk9、LDL-R蛋白表达增加(P<0.05或P<0.01),肝组织 To explore the effect of Buyang huanwu decoction on the lipid level and SREBP-2/Pcsk9 signaling in hyperlipidemia golden hamster(Mesocricetus auratus).Methods Sixty animals were randomly divided into six groups by random number table method:normal group,model group,Buyang huanwu decoction groups including 5,10,20g/kg dose subsets,simvastatin group(0.01g/kg),each had 10 individuals.The normal group was given common feed.The other groups were first fed with high-fat diet to construct a hyperlipidemia model.Four weeks later,the corresponding drugs were given by intragastric administration,but the normal group and model group were administrated an equal volume of distilled water 1 times a day for 4 weeks instead.After the last administration,levels of total serum cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and aspartate aminotransferase(AST),alanine aminotransferase(ALT)were measured,liver histopathology and oil red O staining were performed,protein expression levels of SREBP-2,Pcsk9 and low density lipoprotein receptor(LDL-R)in liver tissues were detected by Western blot.Results Compared to the normal group,the serum levels of TC,TG,LDL-C,AST and ALT in the model group increased significantly[TC:(20.64±4.98)vs(1.31±0.23),TG:(19.20±6.88)vs(0.65±0.01)mmol/L,LDL-C:(17.91±2.69)vs(1.35±0.28)mmol/L,AST:(193.47±28.53)vs(25.37±5.58)U/L,ALT:(146.57±37.10)vs(47.43±14.52)U/L,P<0.01],HDL-C level decreased[(1.06±0.48)vs(3.64±0.74)mmol/L,P<0.01],and the expression of SREBP2,Pcsk9 and LDL-R protein decreased(P<0.05 or P<0.01).Fatty infiltration in liver tissue was obvious,fat vacuoles increased significantly,and lipidosis.Compared to the model group,TC,TG,LDL-C,AST and ALT levels in 10 and 20g/kg dose groups decreased[TC:(16.07±2.68),(8.58±3.57)vs(20.64±4.98)mmol/L,TG:(12.42±3.60),(9.83±2.60)vs(19.20±6.88)mmol/L,LDL-C:(10.16±3.14),(13.86±2.56)vs(17.91±2.69)mmol/L,ALT:(134.13±51.15),(107.21±56.32)vs(193.47±28.53)U/L,AST:(130.55±47.4
作者 王微 刘莉 WANG Wei;LIU Li(Dispensary of traditional Chinese medicine,Hangzhou Red Cross Hospital,Hangzhou,310006,China;Department of Gastroenterology,Hangzhou Red Cross Hospital,Hangzhou,310006,China)
出处 《浙江中西医结合杂志》 2018年第12期1000-1003,1008,1078,共6页 Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
关键词 金黄地鼠 高脂血症 补阳还五汤 SREBP-2 PCSK9 Mesocricetus auratus Hyperlipemia Buyang huanwu decoction SREBP-2 Pcsk9
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