姜黄素对动脉粥样硬化兔基质金属蛋白酶9的影响

目的研究姜黄素对动脉粥样硬化兔主动脉基质金属蛋白酶9表达的影响。方法将30只雄性日本大耳白兔给予高脂饲料喂养2个月。成功复制动脉粥样硬化模型兔20只,随机分成两组,治疗组给予姜黄素200mg/(kg·d)灌胃,对照组每日给予生理盐水灌胃,均以基础饲料喂养,共治疗1月。采血检测血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平变化;兔处死后取主动脉观察粥样斑块面积比;取主动脉弓做病理切片,进行光镜检查,用免疫组织化学检测主动脉壁基质金属蛋白酶9的表达。结果姜黄素治疗组血浆甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平与对照组相比显著降低,高密度脂蛋白胆固醇水平显著升高(P<0.05)。姜黄素治疗组斑块面积/主动脉面积比显著低于对照组(P<0.05),基质金属蛋白酶9免疫组织化学染色强度、阳性细胞率、总积分均低于对照组。结论姜黄素可以显著降低动脉粥样硬化兔主动脉壁基质金属蛋白酶9的表达,抑制动脉粥样硬化的形成。

Effect of Curcumin on the Expression of Matrix Metalloproteinase-9 in the Aorta Atherosclerotic Rabbits

Aim To investigate the effect of curcumin on the expression of matrix matalloproteinase-9 in the aorta atherosclerotic rabbits. Methods Thirty male Japanese White rabbits were fed with high-cholesterol diet for two consecutive months. After atherosclerotic model was established, the remaining animals were randomly divided into two groups: the control group and treatment group. Both groups were fed with standard diet for next one month. Additionally, the treatment group received an oral curcumin at dose 200 mg/kg, and the control group received an oral curcumin-free sodium chloride solution daily during experiment. Before and after the curcumin therapy period, the blood sample were collected in both groups. Serum was separated and used for the assessment of total cholesterol, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) and triglyceride. After three months, all animals were killed. Entire aortas were rapidly dissected out, and the ratio of atherosclerotic plaque was examined. The aortic arch was selected for histological examinations and stained with hematoxylin and eosin (H & E). The expression of MMP-9 was examined with semiquantitative analysis immunohistochemistry in the aorta. Results Both treatment and control group had eight rabbits for analysis. After curcumin treatment for one month, compared with the control group, the treatment group decreased serum triglyceride by 23.5% (0.75±0.15 mmol/L vs 0.98±0.20 mmol/L, P=0.024), total cholesterol by 21.6% (3.52±0.66 mmol/L vs 4.49±0.80 mmol/L,P=0.020) and LDLC by 30.3% (2.05±0.43 mmol/L vs 2.94±0.72 mmol/L,P=0.009), but increased HDLC by 16.3% (1.14±0.15 mmol/L vs 0.98±0.14 mmol/L,P=0.040). Curcumin inhibited the atherosclerotic development in experimental rabbits, the ratio of plaque with area reduced obviously in treatment group as compared to those of control group (22.61%±7.95% vs 42.28%±19.34%,P=0.025). The stained intensity, ratio of positive cell and total score of MMP-9 immunohistochemistry expression were significantly lower in treatment group than those in control group. Conclusion Curcumin could decrease the expression of matrix metalloproteinase-9 in the aorta and attenuate atherosclerotic development in rabbits.