具高血脂藥阻抗性病人接受低劑量Rosuvastatin治療三個月後血清血脂值及基質金屬蛋白酶活性相關性變化探討

Evaluation the correlation of serum lipid profile and MMP activities in difficult-to treat hyperlipidemia patients treated with low-dose Rosuvastatin

陳鳳鴒(Fong-Lin Chen)

指導教授 ： 劉哲育

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2007年)

摘要

高血脂症是引發心血管疾病的重要危險因子。血清中基質金屬蛋白酶(MMP)含量也與冠狀動脈疾病有關。有效控制身體血脂值，可降低引起冠心病(CHD)及糖尿病(DM)患者死亡的風險。但臨床發現，仍然有部份高血脂患者在接受飲食控制及藥物治療後，其血脂值無法有效控制在目標範圍下。本實驗收集90位過去曾服用降血脂藥物而未達到目標值之患者，給予新的statin類降血脂藥物，Rosuvastatin (5mg/day)。觀察患者服藥三個月後血清中-總膽固醇(T.CHO)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)、三酸甘油酯(TG)濃度及其他生化值變化；並利用Gelatin Zymography 方法觀察患者MMP-2,9的活性變化。在接受5 mg Rosuvastatin 治療後，有76位高血脂患者完成三個月的療程，發現服藥後患者血清中平均T.CHO、LDL-C、TG濃度有效降低17.4% (p < 0.001)、25.5% (p < 0.001)及14% (p = 0.056)；HDL-C則提高4.1%。統計結果發現，藥前血清中T.CHO在小於200 mg/dL之患者，藥後MMP-9的活性反而上升且比大於240 mg/dL之患者高(correlation p = 0.02)；具有CHD或DM之高血脂患者，其藥後MMP-9的活性也比無兩病症患者較高(p= 0.011)。本實驗發現低劑量(5mg) Rosuvastatin確實對具高血脂藥阻抗性病人具有有效降低血脂的作用，亦可減緩T.CHO在大於240 mg/dL之患者血清中MMP-9活性；但對於同時具有CHD或DM的高血脂患者，或血脂T.CHO在200 mg/dL以下者，則建議需進一步評估長期服用Rosuvastatin後，MMP-9活性是否增加及伴隨可能的影響。

關鍵字

高血脂症 ； 基質金屬蛋白酶

並列摘要

Hyperlipidemia is a major risk factor of coronary heart disease (CHD). Serum matrix metalloproteinase’s (MMP’s) levels have been related to clinical outcomes in patients with cardiovascular diseases. Randomized clinical trails have demonstrated that reduce serum lipoproteins and cholesterol can significantly decrease CHD risk. However, many patients treated with lipid-lowering drug still can not meet their treatment goals. In this study, we give another new statin agent, Rosuvastatin to 90 difficult-to-treat hyperlipidemia patients with 5 mg per day for 3 months, and 76 patients have completed this process. Then, evaluate the serum total cholesterol (T.CHO), LDL-C, high-density lipoprotein cholesterol (HDL-C) triglycerides (TG), and others biochemical markers concentration changes. The MMP activity examined by Gelatin zymography assay, data show that Rosuvastatin 5 mg effectively reduces the LDL-C (-25.5%, p < 0.001 ), T.CHO (-14.7%, p <0.001 ), TG (-14%) and increases HDL-C (+4.1%) level. There are no statistic significantly changes of GOT, GPT, CPK, hs-CRP, creatinine, and MMP-2,9 activities. However, the T.CHO level<200 mg/dL patients show significantly MMP-9 activities increase after treated with Rosuvastatin (correlation p = 0.02). Besides, the MMP-9 activity is highly increase in patients who combine with CHD and/or DM compare to none CHD and DM patients. These results demonstrate that 5 mg Rosuvastatin treated produces favorable effects on difficult-to-treat hyperlipidemia patients to achieve lipid-lowering goals, but patients who has T.CHO level < 200 mg/dL or with CHD and DM need to observe the risk of MMP-9 activity elevation after taking 5 mg Rosuvastatin for a long time further.

並列關鍵字

Rosuvastatin ； Statin ； Hyperlipidemia ； Matrix metalloproteinase

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