| 王微.补阳还五汤对高脂血症金黄地鼠血脂水平及SREBP-2/Pcsk9信号通路的影响[J].浙江中西医结合杂志,2018,28(12): |
| 补阳还五汤对高脂血症金黄地鼠血脂水平及SREBP-2/Pcsk9信号通路的影响 |
| Effects of Buyang Huanwu decoction on lipid levels and signal pathway of SREBP-2 / Pcsk9 in Golden hamster |
| 投稿时间：2018-07-21 修订日期：2018-10-25 |
| DOI： |
| 中文关键词: 高脂血症 金黄地鼠 补阳还五汤 SREBP-2 Pcsk9 |
| 英文关键词:Hyperlipidaemia Golden hamster Buyang Huanwu decoction SREBP-2 Pcsk9 |
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| 中文摘要: |
| 目的：研究补阳还五汤对高脂血症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：将60只金黄地鼠随机分为正常组、模型组、补阳还五汤5、10、20g/kg组、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，每天一次，连续给药4周。末次给药后，检测各组地鼠血清中总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、谷草转氨酶（AST）、谷丙转氨酶（ALT），肝脏组织病理变化及油红O染色，肝脏组织中SREBP-2、Pcsk9、低密度脂蛋白受体（LDL-R）蛋白表达。结果：与正常组相比，模型组地鼠血清TC、TG、LDL-C、AST、ALT含量增加[（20.64±4.98）mmol/L比（1.31±0.23）mmol/L，（19.20±6.88）mmol/L比（0.65±0.01）mmol/L，（17.91±2.69）mmol/L比（1.35±0.28）mmol/L，（193.47±28.53）U/L比（25.37±5.58）U/L，（146.57±37.10）U/L比（47.43±14.52）U/L，P＜0.01]，HDL-C含量降低[（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。与模型组相比，补阳还五汤10、20g/kg组地鼠血清TC、TG、LDL-C、AST、ALT含量降低[（16.07±2.68）mmol/L、（8.58±3.57）mmol/L比（20.64±4.98）mmol/L，（12.42±3.60）mmol/L、（9.83±2.60）mmol/L比（19.20±6.88）mmol/L，（10.16±3.14）mmol/L、（13.86±2.56）mmol/L比（17.91±2.69）mmol/L，（134.13±51.15）U/L、（107.21±56.32）U/L比（193.47±28.53）U/L，（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含量升高[（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），且肝脏组织脂肪空泡减少，脂质沉积减少；辛伐他丁组地鼠血清TC、TG、LDL-C、AST、ALT含量降低[（10.36±3.24）mmol/L比（20.64±4.98）mmol/L，（10.07±1.92）mmol/L比（19.20±6.88）mmol/L，（10.84±3.41）mmol/L比（17.91±2.69）mmol/L，（118.20±40.64）U/L比（193.47±28.53）U/L，（83.19±30.31）U/L比（146.57±37.10）U/L，P＜0.05或P＜0.01]，HDL-C含量升高[（2.67±0.49）mmol/L比（1.06±0.48）mmol/L，P＜0.05或P＜0.01]，SREBP2、LDL-R蛋白表达增加（P＜0.05或P＜0.01），但对Pcsk9蛋白的表达无差异，肝脏脂肪变性有一定程度的改善。结论：补阳还五汤具有降血脂作用，并改善肝脏组织脂肪变性，促进肝脏脂质代谢，其机制可能与激活SREBP-2/Pcsk9信号通路有关。 |
| 英文摘要: |
| Objective:To study the effects of Buyang Huanwu Decoction on blood lipid levels and SREBP-2/Pcsk9 signaling pathway in golden hamsters with hyperlipidemia. Methods: Sixty golden hamsters were randomly divided into normal group, model group, Buyang Huanwu Decoction 5, 10, 20 g/kg group, simvastatin (0.01 g/kg) group, 10 rats in each group. The normal group of hamsters were given normal feed, and the other groups of hamsters were given high-fat diet to establish a hyperlipidemia model. After 4 weeks, the corresponding drugs were given by intragastric administration. The normal group and the model group were given an equal volume of distilled water once a day. Continuous administration for 4 weeks. After the last administration, total 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 in the serum of each group of hamsters,liver histopathological changes and oil red O staining, SREBP2, Pcsk9, low density lipoprotein receptor(LDL-R) protein expression in liver tissue. Results: Compared with the normal group, the serum levels of TC, TG, LDL-C, AST and ALT in the model group were increased(20.64±4.98mmol/L vs 1.31±0.23mmol/L,19.20±6.88mmol/L vs 0.65±0.01mmol/L,17.91±2.69mmol/L vs 1.35±0.28mmol/L,193.47±28.53U/L vs 25.37±5.58U/L,146.57±37.10U/L vs 47.43±14.52U/L,P＜0.01), the serum levels of HDL-C was decreased(1.71±0.44mmol/L,2.26±0.52mmol/L vs 1.06±0.48mmol/L,P＜0.05或P＜0.01), and the expression of SREBP2, Pcsk9 and LDL-R protein was decreased (P<0.05 or P<0.01). Liver tissue fat infiltration is obvious, fat vacuoles are significantly increased, and lipid deposition. Compared with the model group, the serum levels of TC, TG, LDL-C, AST, ALT in the 10 and 20 g/kg group of Buyang Huanwu Decoction were decreased(16.07±2.68mmol/L,8.58±3.57mmol/L vs 20.64±4.98mmol/L,12.42±3.60mmol/L,9.83±2.60mmol/L vs 19.20±6.88mmol/L,10.16±3.14mmol/L,13.86±2.56mmol/L vs 17.91±2.69mmol/L,134.13±51.15U/L,107.21±56.32U/L vs 193.47±28.53U/L,130.55±47.49U/L,92.01±33.52U/L vs 146.57±37.10U/L,P＜0.05 or P＜0.01), the serum levels of HDL-C(1.71±0.44mmol/L,2.26±0.52mmol/L vs 1.06±0.48mmol/L,P＜0.05 or P＜0.01])and SREBP2, Pcsk9, LDL-R protein expression were increased (p<0.05 or p<0.01), and liver tissue fat vacuoles decreased, lipid deposition decreased. The serum levels of TC, TG, LDL-C, AST and ALT in simvastatin group were decreased(10.36±3.24mmol/L vs 20.64±4.98mmol/L,10.07±1.92mmol/L vs 19.20±6.88mmol/L,10.84±3.41mmol/L vs 17.91±2.69mmol/L,118.20±40.64U/L vs 193.47±28.53U/L,83.19±30.31U/L vs 146.57±37.10U/L,P＜0.05 or P＜0.01), the serum levels of HDL-C was increased(2.67±0.49mmol/L vs 1.06±0.48mmol/L,P＜0.05 or P＜0.01), and the expression of SREBP2 and LDL-R protein was increased (p<0.05 or p<0.01), but there was no difference in the level of Pcsk9 protein expression, and liver steatosis was improved to some extent. Conculsion: Buyang Huanwu Decoction has the effect of lowering blood fat and improving liver tissue steatosis and promoting liver lipid metabolism. The mechanism may be related to the activation of SREBP-2/Pcsk9 signaling pathway. |
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