不同孕期及有無B肝帶原者孕婦血清中生化數值及基質金屬水解酵素-2和-9之活性分析

懷孕時母體上的所有系統尤其以內分泌以及新陳代谢系統都會因胎兒的到來，而產生不同程度的變化。已知基質金屬蛋白水解酵素（matrix metalloproteinases；MMPs）參與胚胎及成體多種生長修護反應，而gelatine更是ECM 中最主要的組成物質，因此基質金屬蛋白水解酵素中之gelatinases（MMP–2、MMP–9） 也被視為胚胎及成體成長修護的重要酵素。然而雖金屬蛋白水解酵素的活性和分泌在許多過程中都有研究，唯獨在懷孕過程中的表現則仍甚少討論。因此為了探討懷孕過程中生理的改變所造成的影響，首先我們收集40位孕婦血清依類別及時間，將實驗組檢體分成孕期2個月孕婦、孕期7個月孕婦血清檢體，探討母體在正常懷孕過程中血清內臨床生化數值相關性及MMP -2和MMP-9活性。發現臨床生化項目的檢查中， Cholesterol（總膽固醇）、LDL-C（低密度脂蛋白）及LDH（血清乳酸脫氫酶）之檢驗數值在孕婦後期顯著升高。雖MMP-2活性表現量沒有太大的差異，但發現孕婦MMP-9活性表現量比非孕婦高，說明懷孕的變化的過程中MMP-9活性表現量受到影響。且懷孕二個月孕婦MMP-9活性表現量是高於孕期七個月孕婦MMP-9活性表現量，顯示懷孕末期MMP-9活性表現量日漸趨緩，說明母體對懷孕產生的變化漸趨適應。同時已知血清內MMP-2與MMP-9的變化與B型肝炎患者轉變為肝硬化甚至肝癌具有絕對相關，因此我們想進一步探討懷孕過程中，是否對於B型肝炎疾病所誘發之MMPs有所影響。我們收集B型肝炎患者孕婦15人與B型肝炎患者非孕婦26人血清，以Gelatin zymography檢測血清中MMP-2、MMP-9活性，發現B型肝炎患者其血清中MMP-2活性表現量有明顯的增加，但B型肝炎患者孕婦血清中之MMP-2活性表現量則與正常人相近；同時B型肝炎患者與B肝孕婦血清中MMP-9活性表現量皆有明顯的增加，顯示出B型肝炎會誘導或增加MMP-9活性表現。但B型肝炎患者血清中MMP-9活性表現量較懷孕的B型肝炎患者血清中MMP-9活性表現量高，顯示懷孕之過程影響B型肝炎所誘導之MMP-9活性表現。結果顯示B型肝炎感染促進了血清中MMP-9活性，且懷孕之過程具有保護及減緩B型肝炎對宿主的傷害作用。

In order to accommodate the arrival of newborns, pregnancy leads to various degrees of changes to mother’s body. The main changes include changes in endocrine system and body metabolism. Numerous published literatures indicated that matrix metalloproteinases MMPs is involved in significant number of physiological reactions. Such as embryo development and adult system repair. Since gelatin is the most critical substance in ECM, and gelatinases (MMP-2, MMP-9) is considered as the most important MMPs. The activity and secretion of matrix metalloproteinases in diverse metabolic pathways have been investigated; however, the expression of MMP during pregnancy was rarely discussed. In order to examine the influence of physiological changes and MMP activity during pregnancy, serum samples from 40 pregnant women were collected. Based on category and time frame, the samples were classified into 2-month and 7-month pregnant serum sample to investigate the changes in MMP-2 and MMP-9 activities in mothers, and possible trends with respect to clinical biochemistry data. Clinical biochemistry data indicated that cholesterol, LDL-C(low density lipoprotein-cholesterol) and LDH (lactate dehydrogenase) elevated to significant level during the latter stage of pregnancy. No significant difference was observed in the MMP-2 activity level of pregnant women in different trimesters and health individuals. However,the MMP-9 activity in pregnant women was higher than those who were not pregnant, suggesting changes during pregnancy would influence the activity level of MMP-9. Besides, MMP-9 activity level in 2-month pregnant women is higher than those 7-month pregnant, suggesting that certain adaptive mechanism during the progress of pregnancy caused the gradual decline of MMP-9 activity level. We already known that changes of MMP-2 and MMP-9 in serum of hepatitis B infected patients can used as an indicator for hepatitis progressing into cirrhosis or even liver cancer. Therefore, the effect of pregnancy on hepatitis B infected liver disease induced MMPs was investigated. Serum samples were collected from hepatitis B patients who were pregnant and not pregnant. Activity level of MMP-2 in hepatitis B patients showed significant increase; yet, when comparing the MMP-2 activity level in pregnant hepatitis B patients and health individuals, it was observed that MMP-2 activity levels in serum of pregnant hepatitis B patients was comparable to the health individuals.In addition, MMP-9 activity level in serum demonstrated significant increase in both pregnant hepatitis B patients and hepatitis B patients, indicating that hepatitis B would induce or increase the activity level of MMP-9. Nevertheless, MMP-9 activity level in hepatitis B patients was higher than those who were pregnant, implying that pregnancy would modulate the activity level of hepatitis B-induced MMP-9.Taken together,the activity level of MMP-9 in serum would increase due to hepatitis B infection; moreover, pregnancy status would modulate the effect of hepatitis B on the host.