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    請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/422


    題名: 白虎湯分期治療大鼠敗血症之研究;Study of Treatment Effects of Bai-Hu-Tang Administered at Early and Late Stage in Septic Rats
    作者: 李承鴻;Cheng-Hung Lee
    貢獻者: 中國醫藥大學:中國醫學研究所碩士班
    關鍵詞: 敗血症;盲腸結紮與穿孔手術;白虎湯;介白素6;介白素10;sepsis;cecal ligation and puncture (CLP);cytokines;interleukin (IL)-6;interleukin (IL)-10;Bai-Hu-Tang
    日期: 2009-07-28
    上傳時間: 2009-08-10 16:01:26 (UTC+8)
    摘要: 在過去兩千多年的中醫藥發展歷史當中,白虎湯被廣泛的運用於治療早期急性感染性疾病合併出現全身系統性發炎反應。本研究的目的即是在探索白虎湯對大鼠敗血症的治療效應,同時也將探討白虎湯對敗血症大鼠血清中細胞激素濃度的調控作用,包含發炎細胞激素,介白素6以及抗發炎細胞激素,介白素10。而上述兩種細胞激素目前皆己被證實為影響敗血症病程進展的演重要因子。
    本研究中共計有36隻大鼠隨機分配至6組,分別是假手術組、敗血症控制組、早期低劑量白虎湯治療組、早期高劑量白虎湯治療組、晚期低劑量白虎湯治療組及晚期高劑量白虎湯治療組。除假手術組外,各組大鼠皆接受盲腸結紮及穿孔手術以引發大鼠敗血症。早期接受低劑量(0.45 g/kg)和高劑量(0.9 g/kg)白虎湯治療之大鼠,分別於敗血症造型後6小時經腸道給予不同劑量之白虎湯。而晚期接受低劑量(0.45 g/kg)和高劑量(0.9 g/kg)白虎湯治療之大鼠,則分別在敗血症造型後12小時經腸道給予不同劑量之白虎湯。假手術組和敗血症控制組則在術後6小時經腸道給予1ml之生理食鹽水以作為治療對照。而在大鼠在手術前和術後4,8,12小時,分別接受抽血,以作為介白素6和介白素10血清濃度的連續追蹤測量和變化分析。所有大鼠皆連續觀察3天以評估其存活率。
    本研究之結果顯示:各組大鼠術前血清中介白素6和介白素10濃度並無差異。而早期接受高劑量白虎湯治療的敗血症大鼠相較於未接受治療的敗血症大鼠,有著顯著較高的3天存活率(80%)和顯著較低的術後12小時血清介白素6和介白素10濃度。同時利用Cox proportional hazards models來評估不同劑量白虎湯治療和敗血症大鼠存活率之間的因果關係。在校正前,單變量之Cox proportional hazards model顯示高劑量白虎湯和較低的死亡涉險率有顯著的相關性(hazard ratio:0.08, p = 0.025)。再將介白素6和介白素10的血清濃度變化納入多變量模型校正後,我們發現血清介白素6的濃度變化是惟一顯著的存活預測因子。而上述的結果意謂著:高劑量白虎湯是經由調控血清中的介白素6濃度來達到改善敗血症大鼠3天存活率的效應。根據本研究結果,傳統方劑白虎湯在未來可能成為臨床治療敗血症的選擇之一!

    Bai-Hu-Tang (BHT) has been broadly applied on treating the early stage of acute infection with systemic inflammation for 2 thousands years in Chinese medicine. We aimed to explore whether BHT is beneficial in treating sepsis and its effects on pro-inflammatory cytokine, interleukin (IL)-6, and anti-inflammatory cytokine, IL-10, which both play important roles in progress of sepsis.
    Thirty-six male Sprague-Dawley rats were randomized into six groups and cecal ligation and puncture (CLP) was performed in all except for the sham-control group. Rats in CLP+BHT-L6 and CLP+BHT-H6 groups receiv- ed a low dose (0.45 g/kg) and a high dose (0.9 g/kg) of BHT, respectively, 6 hrs postoperatively. CLP+BHT-L12 and CLP+BHT-H12 groups received a low and a high dose of BHT, respectively, 12 hrs post- operatively. Sham- control and sepsis-control groups received distilled water (1mL) as vehicle 6 hrs postoperatively. Serial blood samples were drawn before operation, as baseline, and at 4, 8, and 12 hrs postoperatively for IL-6 and IL-10 assay. All rats were monitored for 3 days for survival study.
    Baseline IL-6 and IL-10 were similar in all groups. Rats in the CLP+BHT-H6 group had significantly higher survival rate (80%) and signi- ficantly lower levels of both IL-6 and IL-10 at 12 hrs postoperatively than those in the sepsis-control group. Cox proportional hazards models were used to evaluate the cause and effect between different doses of BHT and survival. Before adjustment, univariate Cox proportional hazards model revealed early administration of high dose BHT was associated with signi- ficantly decreased risk of death (hazard ratio: 0.08, p = 0.025). After adding changes of IL-6 and IL-10 into the model, change of IL-6 was the only pre- dictor for survival indicating that early administration of high dose BHT improved survival by reducing IL-6 level.
    The results suggested the ancient formula BHT may be a promising complementary therapy for sepsis.
    顯示於類別:[中國醫學研究所] 博碩士論文

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