滇黄芩黄酮的调脂保肝作用及其对肝组织HMGCR、CYP7A1活性影响的研究

Study on the Lipid-regulating and Liver-protecting Effects of Flavonoids from Scutellaria Amoena and the Effects on the Activities of HMGCR and CYP7A1 in Liver Tissue

关键词:  高脂血症大鼠  滇黄芩黄酮  调脂保肝  羟甲基戊二酰辅酶A还原酶  胆固醇7α-羟化酶

Key words:  hyperlipidemia rats  Scutellaria amoena flavonoids  lipid-regulating and liver-protecting  HMGCR  CYP7A1

摘要:

目的 研究滇黄芩黄酮(Scutellaria amoena flavonoids，SAF)对高脂血症大鼠的调脂保肝作用及其对肝组织中羟甲基戊二酰辅酶A还原酶(HMG-Co A reductase，HMGCR)、胆固醇7α-羟化酶(cholesterol 7α-hydroxylase，CYP7A1)活性的影响。方法 40只SD大鼠随机选取8只作为正常组，32只通过高脂饮食诱导建立高脂血症大鼠模型。8周后高脂血症大鼠随机分为模型组(生理盐水)，非诺贝特组(20 mg·kg^-1)，SAF高、低剂量组(100，20 mg·kg^-1)，每天1次，连续给药4周。每周监测动物体质量变化，处死动物后测定其血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和肝脏中TC、TG的含量，HE染色法观察大鼠肝组织病理形态学变化，ELISA检测肝组织HMGCR、CYP7A1的活性。结果 与正常组相比，模型组大鼠的体质量、血清中TC、TG、LDL-C、ALT、AST显著升高，HDL-C显著降低(P<0.001)，肝脏脂肪变性明显，肝组织中TC、TG含量和HMGCR活性显著升高、CYP7A1活性显著降低(P<0.001)；与模型组相比，SAF高、低剂量组均能显著降低高脂血症大鼠体内TC、TG、LDL-C、ALT、AST水平，升高HDL-C水平(P<0.05或P<0.001)，肝组织病理学明显改善，肝组织中TC、TG含量和HMGCR活性显著降低，CYP7A1活性显著升高(P<0.01或P<0.001)，其中高剂量组差异更为显著。结论SAF能显著降低高脂血症大鼠体内血脂水平，改善肝功能，其作用机制可能是通过下调HMGCR水平，提高CYP7A1活性抑制胆固醇的生物合成，进而调节脂质代谢紊乱。

Abstract:

OBJECTIVE To study the effect of Scutellaria amoena flavonoids(SAF) on regulating lipid and protecting lilver and the activities of HMG-Co A reductase(HMGCR) and cholesterol 7α-hydroxylase(CYP7A1) in hyperlipidemia rats. METHODS Eight rats were randomly selected from 40 SD rats as the normal group, 32 hyperlipidemia model rats were induced by high-fat diet. After 8 weeks, hyperlipidemia rats were divided randomly into model group(saline), fenofibrate group(20 mg·kg^-1), SAF high and low dose groups(100, 20 mg·kg^-1), and 1 time per day for 4 consecutive weeks. Body weights was checked every week. At the end of the experiment, the contents of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), aspartate aminotransferase(AST), alanine aminotransferase(ALT) in serum and TC, TG in liver were measured. The histopathological changes of the liver tissues were observed by HE staining. The activities of HMGCR and CYP7A1 in the liver tissues were detected by ELISA. RESULTS Compared with the normal group, the results showed that the model group significantly increased body weight, and the levels of TC, TG, LDL-C, ALT and AST in serum, while HDL-C level was decreased(P<0.001). In liver tissue, steatosis was severe, and the levels of TC, TG and the activity of HMGCR were significantly increased, while the activity of CYP7A1 was significantly decreased(P<0.001). Compared with the model group, the results showed SAF high and low dose groups significantly reduced the levels of TC, TG, LDL-C, AST, ALT, while significantly increased the level of HDL-C in serum(P<0.05 or P<0.001). In liver tissue, the pathological changes were improved, and the levels of TC, TG and the activity of HMGCR were significantly reduced, while the activity of CYP7A1 was significantly increased after SAF administration(P<0.01 or P<0.001), especially in high dose group. CONCLUSION The SAF can significantly reduce blood lipid level of hyperlipidemia rats, while it can improve liver function. The mechanism might be related to the down-regulation of HMGCR level to inhibit cholesterol biosynthesis and the up-regulation of CYP7A1 activity to promote cholesterol metabolism, which regulate lipid metabolism disorder.