Splanchnic Hyposensitivity to Glypressin in a Hemorrhage-Transfused Rat Model of Portal Hypertension: The Role of Tumor Necrosis Factor-α

腫瘤壞死因子在出血－輸回模式門脈高壓老鼠glypressin低敏感性所扮演之角色

黃惠君(Hui-Chun Huang) ； 王聖賢(Sun-Sang Wang) ； 李發耀(Fa-Yauh Lee) ； 張扶陽(Full-Young Chang) ； 林漢傑(Han-Chieh Lin) ； 侯明志(Ming-Chih Hou) ； 李壽東(Shou-Dong Lee)

《臺灣消化醫學雜誌》 24卷2期 (2007/06) Pp. 165-172

https://doi.org/10.6557/GJT.200706_24(2).0001

摘要

研究動機，使用血管升壓素(vasopressin)及其長效類似物glypressin於急性出血之門脈高壓動物或肝硬化病人時，其降門脈壓作用，較未出血者不明顯，此現象稱為內臟血管對血管收縮劑之低敏感性(splanchnic hyposensitivity)。過去之研究，發現氣化氮與此血管低敏感性現象有關。而腫瘤壞死因子可刺激氧化氮的合成，並在急性出血時，有表現增強的現象，但其於門脈高壓急性出血狀態下對血管低反應性所扮演的角色，目前還不清楚。
材料方法：雄性大白鼠以部分門脈結紮導致門脈高壓。於術後十四天，到定系統及門脈血流動力參數，再把老鼠隨機分為出血及不出血組。出血組係以定速幫浦每分鐘抽血0.3ml，歷時十五分鐘，共抽取4.5ml血液，而後以同箏速度輸回原抽取血液的一半，不出血組則於同時間內不做任何處置。四十五分鐘後，第二次利定血流動力學參數，然後輸注glypressin(0.07mg/kg)，十分鐘後第三次到定血流動力學參數，最後抽血測定腫瘤壞死因子之濃度。
結果：門脈高壓老鼠於急性出血時腸道血管對glypressin產生低敏感性。血中腫瘤壞死因子之濃度以出血組較高，但尚未達到統計學上的顯著意義（出血vs．不出血組，7.96±0.52vs.6.82±0.38ρg/ml, P=0.087）。
結論：門脈高壓老鼠於急性出血時，腫瘤壞死因子在腸道血管對glypressin的低敏感性上似乎並未扮演重要角色。其他內生性血管反應物質造成的影響應亦列入考慮。

關鍵字

肝門靜脈高壓 ； 長效型血管升壓素 ； 出血 ； 低敏感性 ； 腫瘤壞死因子

並列摘要

Introduction: Vasopressin and its long-acting analogue, glypressin given during hemorrhage are less effective than when given during a stable state in portal hypertensive or cirrhotic conditions, that is, the so-called hyposensitivity phenomenon. According to the previous studies, nitric oxide has been ascribed to participate in the hyposensitivity. Tumor necrosis factor-α stimulates nitric oxide synthesis and is enhanced during acute hemorrhage. However, its role in portal hypertension with acute hemorrhage and vascular hyporesponsiveness remains unclear.
Materials and Methods: Portal hypertension was induced by partial portal vein ligation (PVL) on male Spraque-Dawley rats. Fourteen days after PVL, portal and systemic hemodynamic parameters were evaluated then rats were divided into without-bleeding and with-bleeding groups. In rats with a hypotensive hemorrhage, 4.5ml of blood was withdrawn with an infusion/withdrawal pump, of which 50% was re-infused. The without-bleeding groups received no manipulation during the same period of time. Forty-five minutes later, the second hemodynamic measurement was performed, followed by glypressin (0.07mg/kg) infusion. Ten minutes after glypressin administration, the third hemodynamic study was done, followed by heparinized blood sampling for TNF-α measurements.
Results: splanchnic hyposensitivity to glypressin was noted in portal hypetensive rats during acute hemorrhage. The level of tumor necrosis factor tended to be higher in rats with bleeding but not statistically significant (P=0.087).
Conclusion: Tumor necrosis factor did not seem to play a significant role in splanchnic hyposensitivity to glypressin in portal hypertensive rats during acute hemorrhage. The influences of other endogenous vasoactive substances should also be considered.

並列關鍵字

portal hypertension ； glypressin ； hemorrhage ； hyposensitivity ； tumor necrosis factor