- 學位論文
人參皂苷萃取物及人參皂苷Rb1對四氯化碳誘發大鼠 肝發炎反應及纖維化之影響
Effects of Panax ginseng ginsenoside extract and ginsenoside Rb1 on CCl4-induced liver inflammation and fibrosis in rats
摘要
近年來，慢性肝炎及肝硬化已成為台灣十大死因之第七位，且研究指出肝癌之發生與肝炎及肝硬化有關，因此，本研究目的在於探討人參萃取物及人參皂苷Rb1對四氯化碳誘發老鼠肝損傷發炎反應及肝纖維化之影響。將老鼠隨機分成四組：控制組 (正常飲食＋腹腔注射橄欖油)、CCl4組 (正常飲食＋腹腔注射CCl4)、人參皂苷萃取物組 (人參皂苷萃取物＋腹腔注射CCl4)、人參皂苷Rb1組 (人參皂苷Rb1＋腹腔注射CCl4)。人參皂苷萃取物為80%人參皂苷，含8種人參皂苷 (Rh1、Rh2、Rg1、Rg2、Rg3、Rd、Rc、Rb1) ，人參皂苷Rb1純度為98%，分別以0.05%及0.005% (w/w) 之比例添加於飼料中。實驗為期九週，每週給予每公斤體重0.75 mL之40% CCl4，一週一次共給予八次；控制組則注射同等劑量之橄欖油。九週後進行犧牲並採集血液樣本及肝組織，進行病理組織切片、肝功能指標、脂質代謝、肝發炎反應指標，及肝纖維化指標之測定分析。病理切片結果顯示，人參皂苷萃取物及人參皂苷Rb1可降低CCl4所造成肝臟脂肪空泡堆積，其效果又以人參皂苷Rb1較為顯著 (p<0.05)；而人參萃皂苷取物可減少肝臟細胞壞死 (p<0.05) 及膠原蛋白堆積的情形。實驗期間，給予人參皂苷萃取物及人參皂苷Rb1能顯著降低因肝損傷而引起glutamate oxaloacetate aminotransferase (GOT)、glutamate pyruvate aminotransferase (GPT) 活性上升之情形 (p<0.05)，且可顯著降低肝臟中三酸甘油酯 (p<0.05) 含量。在發炎反應指標方面，人參皂苷萃取物可顯著降低肝臟中促發炎細胞激素tumor necrosis factor-α、interleukin-1b含量 (p<0.05)，且人參萃取物及人參皂苷Rb1均可顯著降低肝臟prostaglandin E2 濃度 (p<0.05)。纖維化指標方面，人參皂苷萃取物及人參皂苷Rb1均能顯著抑制肝臟中膠原蛋白前驅物-羥基脯胺酸 (hydroxyproline) 含量，及肝臟金屬蛋白酵素組織抑制物-1 (tissue inhibitor of metalloproteinases-1) 濃度 (p<0.05)。因此，給予人參皂苷萃取物及人參皂苷Rb1可降低四氯化碳誘發肝損傷下老鼠血漿GOT、GPT 上升的情形，並降低發炎反應，而達到抑制肝臟纖維化之功能。
並列摘要
Chronic hepatitis has been currently become the 7th leading cause of death in Taiwan, and is associated with the occurrence of hepatocellular carcinoma. This study investigated ginsenosides on carbon tetrachloride (CCl4)-induced hepatitis and fibrosis in rats. Male Sprague-Dawley rats were randomly divided into 4 groups: control, CCl4, CCl4+Panax ginseng ginsenoside extract (GE; 80% ginsenosides with Rh1, Rh2, Rg1, Rg2, Rg3, Rd, Rc, and Rb1), and CCl4+Rb1 (Rb1; 98% Rb1) groups. Rats were intraperitoneally injected with 40% CCl4 at a dose of 0.75 mL/kg body weight once a week for 7 weeks two weeks after oral administration of GE or Rb1 at a dose of 0.05% or 0.005%, respectively. Rats were intraperitoneally injected with an equivalent dosage of olive oil as the control group. After 9-week treatments with ginsenosides, plasma and liver were collected for biochemical and pathological analyses. The pathological results showed that the GE and Rb1 groups significantly reduced hepatic fat deposition (p<0.05), especially the Rb1 group. The GE group decreased hepatic necrosis and collagen accumulation. Both GE and Rb1 treatments reduced plasma glutamate oxaloacetate aminotransferase (GOT) and glutamate pyruvate aminotransferase (GPT) activities during the experimental period, as well as plasma and hepatic triglycerides elevated by CCl4 (p<0.05). The GE group inhibited hepatic pro-inflammatory cytokines: tumor necrosis factor-α, interleukin-1b (p<0.05). Both GE and Rb1 treatments reduced hepatic prostaglandin E2 levels (p<0.05). Both GE and Rb1 decreased hepatic collagen precursor – hydroxyproline and tissue inhibitor of metalloproteinases-1 levels (p<0.05). Therefore, Panax ginseng ginsenoside extract and Rb1 can reduce GOT and GPT activities and moderate hepatic necrosis and inflammation induced by CCl4 to inhibit liver fibrosis.