- 學位論文
丹參酚酸B 對於纖維蛋白原之作用機轉討論
To study Salvianolic acid B on the fibrinogen level for HepG2-TRα1 and the hemorheology parameter for T3 rats.
摘要
甲狀腺素 （Triiodothyronine, T3）是一種可調控細胞生長、發育與分化之重要因子。然而，過量的甲狀腺素會造成血液中纖維蛋白原 （fibrinogen） 上升，促使紅血球聚集度增加，血液黏度提高，造成血液流變異常。丹參 （Salvia miltiorrhiza Bunge） 是一種具有活血化瘀功能的中草藥，被廣泛應用於治療心血管疾病。丹參酚酸B （Salvianolic acid B，Sab） 是丹參水溶性有效成分，因此透過探討丹參酚酸B 對大鼠血液中纖維蛋白原的影響。 利用T3刺激HepG2-TRα1細胞，使其生成纖維蛋白原，再利用不同濃度10、30、50、80、100 μM 丹參酚酸B處理，由Q-PCR及ELISA分別得知纖維蛋白原mRNA及protein生成量，由實驗結果得，以30 μM以上之丹參酚酸B處理，纖維蛋白原mRNA生成量會開始明顯降低；而纖維蛋白原protein層面，則是50 μM以上的丹參酚酸B，可降低纖維蛋白原生成量，因此可推論：丹參酚酸B可抑制纖維蛋白原mRNA生成。 本實驗使用八週齡之Sprague-Dawley 大鼠，給予T4飲用水，於第六週開始，每天分別餵食30、50、80mg/(kg day)丹參酚酸B，持續六週。並抽取其血液檢測血液流變之參數。結果顯示，餵食50、80mg/(kg day)丹參酚酸B組於第四、六週之纖維蛋白原含量較T4組低；於第六週時，紅血球聚集度較T4組低；於低shear rate下，三組餵食丹參酚酸B組相較於T4組其黏度皆有降低之趨勢。纖維蛋白降解產物（FDP）也無明顯差異。由此可知：丹參酚酸B具有降低纖維蛋白原生成之功效。
並列摘要
The thyroid hormone, 3, 3', 5-triiodo-L-thyronine (T3) regulates growth, development and differentiation processes in animals. Nevertheless, excessive T3 will raise the fibrinogen level in the blood established leading to the erythrocyte aggregation increasingly, and enhance the whole blood viscosity, creating the anomaly in hemorheological. Salvia miltiorrhiza Bunge is widely used for the treatment of atherosclerosis-related disorders and known as Danshen in Chinese traditional medicine is effective in promoting circulation and decreasing stasis in the blood. Salvianolic acid B (Sab) is a potent water-soluble from the roots of Salvia miltiorrhiza Bunge. Therefore, to explore the effects of Sab on the fibrinogen mRNA level in the blood for Rats. We first adapt HepG2-TRα1 cell culture and T4 rat animal model in this preliminary study.To study the fibrinogen mechanism after T3 treatment in TRa-overexpressed hepatoma cell line (HepG2-TRa1) and then activate HepG2-TRa1 with 10、30、50、80、100 μM Sab. In addition to fibrinogen mRNA levels evaluate by Q-PCR, the fibrinogen protein was evaluate by ELISA. According to the result , the fibrinogen mRNA levels were decrease after the treatment of 30 μM Sab, and in the fibrinogen protein levels, it is significant decrease in the 50 μM Sab. The results indicate that Sab can inhibite the release of fibrinogen mRNA. In the in vivo study, we selected the 8-week-old Sprague-Dawley rat as the animal experimental models and fed them a diet containing L-thyroxine for 6 weeks and then fed them 30、50、80mg/(kg day) of Sab for 6 weeks, respectively, in order to evaluate the hemorheological parameters.The results showed that the fibrinogen levels of the orally given 50、80mg/(kg day) of Sab groups are lower than the T4 group at fourth and sixth week. At sixth week, the same groups showed that the erythrocyte aggregation of the 50、80mg/(kg day) of Sab groups are lower compared with the T4 group. At the low shear rate, except that all of the Sab groups showed that the whole blood viscosity compared with the T4 group decreased. The FDP values was not significant in all of the groups. The results indicate：Sab might play an important role in the release of fibrinogen mRNA.