臺灣博碩士論文加值系統

本實驗目的主要是研究清醒WKY大白鼠經靜脈及腦室給予內毒素(lipopolysaccharide，LPS)產生敗血症生理反應的過程，包括週邊及中樞24小時內的全身動脈壓、心跳、一氧化氮產生量和感壓反射功能的變化以及相互關係。結果顯示，清醒大白鼠經靜脈注射單一劑量內毒素(10 mg/kg)於15分鐘內血壓迅速下降由對照組128.757.72下降至78.139.59 mmHg (p＜0.05, n=8)，第2小時後回復正常。心跳則反射性的上升，由對照組362.521.11 上升至 427.517.19 bpm (n=8)；心跳速率從第1小時開始有意義的增加至422.514.24 bpm (p＜0.05, n=8) ，在第6小時為最高峰(47011.95 bpm, n=8)；血液中一氧化氮代謝產物產生量在第4小時後有意義的增加，且於第7小時後達最高峰由對照組15.87±5.03上升至357.3±88.11μM (p＜0.05, n=8)，在第24小時有回復現象；然而24小時內的體溫呈現有意義的增加。大白鼠經腦室注射內毒素(LPS 0.004-0.12 mg/100g)，24小時內血壓無太大變化，但心跳速率和一氧化氮產生量隨著LPS時間的愈久和劑量加大就愈增加； LPS 0.04 mg/100g組其心跳和血液中一氧化氮產生量為最大反應劑量(474.4±13.36 bpm, n=15， 194.21±44.05μM, n=11)，然而24小時內的體溫亦呈現有意義的增加；而LPS 0.12 mg/100g組無法存活24小時，其腦脊隨液中一氧化氮代謝產物生成量在第3和6小時有增加現象，但量很小，並無統計上差異。然而24小時內的體溫亦呈現有意義的增加。靜脈注射組的感壓反射功能，在本實驗中，並無發現有被抑制現象；而腦室注射組，以LPS 0.04 mg/100g組為例，反射性心跳速率的變化與血壓大小的乙狀關係（R2）在第3、第6小時和第24小時由對照組0.035減弱為-0.002、-0.053及0.006 (n=8)和反射活性最大利潤由對照組-1.969減弱為0.037、-0.905 及0.282 (n=8)，而最大反射活性（反射活性利潤變化中點）的血壓值有向右移由對照組146 ±3.56向右移至243.5 ±33.80 mmHg (n=8)。為了區分內毒素之抑制是在感壓反射的交感或副交感神經，本實驗將降壓藥物SNP及升壓藥物Phe區分來比較血壓升降時所反應的心跳變化之敏感度。結果顯示，無論是在交感和副交感神經的活性都有可能被抑制，尤其以LPS 0.04組的反應為最明顯，其第3、第6至第24小時SNP 或Phe的感壓反射斜率變化由對照組2.570.53 減少至2.130.42、0.7160.27及1.350.45或2.540.31 減少至2.160.29、3.140.35及2.180.28。
總括這些結果顯示，在實驗中發現，內毒素無論是經由清醒大白鼠靜脈及腦室注射後，一氧化氮產生量增加可能會刺激心跳變快和發燒現象。感壓反射功能的抑制現象在腦室作用較明顯，交感或副交感神經同時被抑制，也可能一氧化氮產生量有密切的關係。

The purpose of this work was to evaluate the process of lipopolysaccharide (LPS)-induced sepsis shock by peripheral and central administration in conscious WKY rats. Changes in mean blood pressure、heart rate、blood NOx products and baroreflex activities were evaluated. In conscious WKY Rats, a single intravenous dose of lipopolysaccharide (LPS 10mg/kg) temporally decreased the mean blood pressure in 15 mins (from 128.757.72 to 78.139.59 mmHg, p0.05, n=8) that recorvered in 2h, and caused a reflex tachycardia; Heart rate constantly and siginificantly increased in 24h that reached maximal in 6h (from 362.521.11 to 47011.95 bpm, p0.05, n=8); NOx increased in 4h and reached maximal in 7h (from 15.875.03 to 357.388.11 M, p0.05, n=8) that recorverd in 24h；Body temperature siginificantly increased in 24hr. Intracerebral administration of LPS in dose range of 0.004-0.12 mg/100g did not significantly change the blood pressure in 24 hours. The heart rate and blood NOx were increased in a dose-dependenct manner that reached maximal level in 6h and recovered after 24h；Body temperature siginificantly increased in 24hr. Intracerebral administration of LPS in dose of 0.04 mg/100g got a maximal response and in dose of 0.12 mg/100g can not survive over 24hr which CSF NOx were slight increased in 3hr and 6hr.
In this study, the baroreflex function was not changed with peripheral administration, but were inhibited with peripheral administration. The maximal gain of baroreflex activity were decreased of rats at a dose of 0.04 mg/100g in 3rd、6rd and 24 rd from —1.969 to 0.037、—0.905 and 0.282 (n=8), and the curve for baroreflex ativity were shifted to the right from 146 ±3.56to 243.5±33.80 mmHg (n=8). In order to distingwish LPS inhibited effects of sympathetic and paresympathetic nerve on baroreflex function, “SNP” and “Phe” would be separate evaluated. We found that no matter sympathetic or paresympathetic were inhibited, especially after LPS 0.04 mg/100g administration in 3rd、6rd and 24rd on SNP or Phe induced baroreflex slope。 It was from 2.570.53 to 2.130.42、0.7160.27 and 1.350.45 (n=8) or from 2.540.31 to 2.160.29、3.140.35 and 2.180.28 m (n=8)。
All these results suggest that the production of NOx might stimulated the heart rate increase and fever in central and peripheral effects after LPS administration. The production of NOx might inhibited the baroreflex activities in central effects after LPS administration.

目錄--------------------------------------------------------I
圖次--------------------------------------------------------III
中文摘要----------------------------------------------------V
英文摘要----------------------------------------------------VII
緒論--------------------------------------------------------1
實驗材料與方法----------------------------------------------5
壹、 實驗動物的來源-----------------------------------------5
貳、 實驗設計流程-------------------------------------------5
參、 手術---------------------------------------------------7
肆、 藥物來源-----------------------------------------------7
伍、 溶劑配製-----------------------------------------------8
陸、 測量內毒素對清醒大白鼠其血壓與心跳之變化---------------8
柒、 感壓反射功能的評估-------------------------------------8
捌、 測量內毒素對清醒大白鼠其血液中一氧化氮的影響-----------9
玖、 實驗統計-----------------------------------------------10
實驗結果----------------------------------------------------11
壹、 靜脈或腦室注射酯多醣體對清醒大白鼠血壓、心跳及血液中一氧化氮的影響----------------------------------------------------11
貳、 腦室注射酯多醣體對清醒大白鼠腦脊隨液中一氧化氮代謝生成量的變化--------------------------------------------------------13
參、靜脈或腦室注射酯多醣體對清醒大白鼠體溫的變化------------14
討論--------------------------------------------------------19
結論--------------------------------------------------------24
參考文獻----------------------------------------------------47
圖次
圖一、清醒大白鼠於靜脈注射單一劑量LPS 10mg/kg後，24小時內血壓的變化--------------------------------------------------------25
圖二、清醒大白鼠於腦室注射ACSF、LPS 0.004-0.12 mg/100g後，24小時內的血壓的變化----------------------------------------------26
圖三、清醒大白鼠於靜脈注射單一劑量LPS 10mg/kg後，24小時內心跳的變化--------------------------------------------------------27
圖四、清醒大白鼠於腦室注射ACSF、LPS 0.004-0.12 mg/100g後，24小時內的心跳的變化----------------------------------------------28
圖五、清醒大白鼠於靜脈注射單一劑量LPS 10mg/kg後，24小時內一氧化氮的變化----------------------------------------------------29
圖六、清醒大白鼠於腦室注射ACSF、LPS 0.004-0.12 mg/100g後，24小時內的一氧化氮的變化------------------------------------------30
圖七、清醒大白鼠於腦室注射LPS 0.12 mg/100g後，7小時內腦脊髓液中一氧化氮的變化----------------------------------------------31
圖八、清醒大白鼠於靜脈注射單一劑量LPS 10mg/kg後，24小時內體溫的變化--------------------------------------------------------32
圖九、清醒大白鼠於腦室注射LPS 0.04 mg/100g後，24小時內的體溫的變化----------------------------------------------------------33
圖十、清醒大白鼠於腦室注射LPS 0.12 mg/100g後，24小時內的體溫的變化----------------------------------------------------------34
圖十一、清醒大白鼠於靜脈LPS 10mg/kg前和後3、6、24小時之感壓反射最大活性利潤變化--------------------------------------------35
圖十二-十六、清醒大白鼠於腦室注射ACSF、LPS 0.004-0.12 mg/100g前和後3、6、24小時之感壓反射最大活性利潤變化------------------36
圖十七、清醒大白鼠於靜脈LPS 10mg/kg前和後3、6、24小時內SNP及Phe分別所造成的感壓反射敏感性變化------------------------------41
圖十八-二十二、清醒大白鼠於腦室注射ACSF、LPS 0.004-0.12 mg/100g前和後3、6、24小時內SNP及Phe分別所造成的感壓反射敏感性變化--42

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