目的 观察山楂叶水提物对同型半胱氨酸（homocysteine，Hcy）和高脂诱导的载脂蛋白E敲除（apolipoprotein E knockout，ApoE^-/-）小鼠血管炎症损伤及机体脂代谢紊乱的影响。方法 取8只正常喂养的C57BL/6J小鼠作为对照组，40只ApoE^-/-小鼠随机分为高脂组、高脂＋甲硫氨酸组、辛伐他汀（5.7 mg/kg）组和山楂叶低、高剂量（12、24 g/kg）组，每组8只。除对照组外，其余小鼠均使用21%高脂饲料喂养18周。从第11周开始，除对照组和高脂组外，其余小鼠每日ig甲硫氨酸（1 g/kg）诱导高Hcy血症。同时各给药组ig相应药物，对照组和高脂组ig等体积的生理盐水。检测小鼠外周血中白细胞、红细胞、血红蛋白和血小板含量；检测小鼠血清中Hcy、总胆固醇（total cholesterol，TC）、三酰甘油（triglyceride，TG）、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）、白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、IL-1β、丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、血肌酐（serum creatinine，SCr）和血尿素氮（blood urea nitrogen，BUN）水平；油红O染色观察小鼠主动脉内壁的脂质斑块及肝脏切片中脂质含量；Filipin染色检测小鼠肝脏中胆固醇含量；苏木素-伊红（hematoxylin-eosin，HE）染色检测小鼠主动脉组织病理形态变化；Masson染色检测小鼠主动脉胶原纤维的沉积；免疫荧光染色检测主动脉p50、p65及肝脏中固醇调节元件结合蛋白1（sterol regulatory element binding protein 1，SREBP1）、SREBP2蛋白表达。结果 与对照组比较，高脂组和高脂＋甲硫氨酸组小鼠血清中Hcy、TC、TG、LDL-C和炎症因子水平显著升高（P＜0.01），HDL-C水平显著降低（P＜0.01）；主动脉红染面积明显增加（P＜0.01），内膜增厚并出现明显病理改变，脂质累积增加（P＜0.01），p50和p65表达增加（P＜0.01）；肝脏SREBP1和SREBP2表达增加（P＜0.01），脂质含量增加（P＜0.01）。与高脂＋甲硫氨酸组比较，各给药组小鼠血清中Hcy、TC、TG、LDL-C和炎症因子水平显著降低（P＜0.01），HDL-C水平显著升高（P＜0.05、0.01）；主动脉红染面积明显减少（P＜0.01），病理改变减轻，脂质累积减少（P＜0.01），p50和p65表达减少（P＜0.01）；肝脏SREBP1和SREBP2表达减少（P＜0.01），脂质含量减少（P＜0.01）。结论 山楂叶水提物能够改善小鼠血管的动脉粥样硬化，其作用机制可能与抑制血管内皮的炎症损伤和肝脏脂质合成密切相关。

Objective To observe the effect of water extract of Crataegus pinnatifida leaves on vascular inflammatory injury and systemic lipid metabolism disorders in apolipoprotein E knockout (ApoE^−/−) mice induced by homocysteine (Hcy) and high fat. Methods Eight C57BL/6J mice fed a normal diet were served as the control group, 40 ApoE^−/− mice were randomly divided into high-fat group, high-fat + methionine group, simvastatin (5.7 mg/kg) group, C. pinnatifida leaves low-and high-dose (12, 24 g/kg) groups, with eight mice in each group. Except for the control group, all other mice were fed a 21% high-fat diet for 18 weeks. Starting from the 11th week, except for the control and high-fat groups, the remaining mice were received daily intragastric administration of methionine (1 g/kg) to induce hyperhomocysteinemia. Corresponding drugs were administered to each treatment group, while the control and high-fat groups received an equivalent volume of saline. Counts of white blood cells, red blood cells, hemoglobin and platelets in peripheral blood were measured. Levels of Hcy, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr) and blood urea nitrogen (BUN) in serum were assessed. Oil red O staining was used to observe lipid plaques in aortic intima and lipid content in liver sections. Filipin staining was used to measure hepatic cholesterol level. Hematoxylin-eosin (HE) staining was used to examine pathological morphological changes in aortic tissue. Masson staining was used to detecte collagen fiber deposition in aorta. Immunofluorescence staining was used to evaluate the expressions of p50, p65 in aorta and sterol regulatory element binding protein 1 (SREBP1) and SREBP2 in liver. Results Compared with control group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in high-fat group and high-fat + methionine group were significantly increased (P < 0.01), while the level of HDL-C was significantly decreased (P < 0.01). The red stained area of aorta was significantly increased (P < 0.01), the endometrium was thickened and showed obvious pathological changes, lipid accumulation was increased (P < 0.01), and expressions of p50, p65 were increased (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were increased (P < 0.01), and the lipid content was increased (P < 0.01). Compared with high-fat + methionine group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in each treatment group were significantly reduced (P < 0.01), while the level of HDL-C was significantly increased (P < 0.05, 0.01). The red stained area of aorta was significantly reduced (P < 0.01), pathological changes were alleviated, lipid accumulation was reduced (P < 0.01), and the expressions of p50, p65 were reduced (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were decreased (P < 0.01), and the lipid content was decreased (P < 0.01). Conclusion The water extract of C. pinnatifida leaves could improve the atherosclerosis of blood vessels in mice, and its mechanism may be closely related to the inhibition of inflammatory damage of vascular endothelium and liver lipid synthesis.

R285.5

国家自然科学基金资助项目（82280659）；甘肃省自然科学基金资助项目（22JR11RA125）；甘肃省高校教师创新基金项目（2026A-102）；西北营养与环境相关疾病中医药防控协同创新中心2025年度开放基金（ZYXT-25-03）