為探討肝臟缺血再灌注損傷過程中血小板激活因子(plateletactivating factor, PAF)及中性粒細胞的作用及其機理,作者在建立大鼠肝臟局部缺血再灌注損傷模型的基礎上,對PAF的變化及中性粒細胞的浸潤程度進行了初步研究,觀察了PAF拮抗劑海風藤酮對大鼠肝臟局部缺血再灌注損傷的保護作用。結果表明:肝臟缺血再灌注損傷時肝組織PAF含量增高,且隨再灌注時間的延長而加重;早期肝組織抗氧化能力下降,大量氧自由基生成,以及細胞內鈣超載是損傷的主要原因,而肝臟Ⅱ相損傷主要是由于肝組織PAF的積聚,激活中性粒細胞,導致溶酶體酶和毒性自由基的產生所致。海風藤酮可以拮抗損傷過程中PAF增高所致的藥理作用,減輕肝臟脂質過氧化程度,改善肝功能,減輕肝臟病變程度。本實驗結果提示:PAF拮抗劑可能為肝臟缺血再灌注損傷的防治提供一條新的途徑。
引用本文: 史留斌,陳懷仁,王爾慧,嵇振嶺. 海風藤酮對大鼠肝臟缺血再灌注損傷保護作用的實驗研究. 中國普外基礎與臨床雜志, 1998, 5(4): 195-198. doi: 復制
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1. | McCord JM. Oxygenderived free redicals in post ischemic tissue injury. New Engl J Med, 1985; 312(3)∶159. |
2. | Kane AB, Young EE, Schanne FAX, et al. Calcium dependence of phalloidininduced liver cell death. Proc Natl Acad Sci USA, 1980; 77(2)∶1177. |
3. | Braquet P, Koltai M, Bourgain R, et al. Is there a care for PAF antagonists in the treatment of ischemic states? TIPs, 1989; 10(1)∶23. |
4. | Gardner CR, Laskin JD, Laskin DL. Plateletactivatingfactor induced calcium mobilization and oxiditive metabolism in hepatic macrophagesand endothelial cells. J Leukoc Biol, 1993; 53(1)∶190. |
5. | Jaeschke H, Farhood A, Smith CW. Neutrophils contribute to ischemia/reperfusion injury in rat liver invivo. FASEB J, 1990; 4(A120)∶3353. |
6. | Shen TY, Hwang SB, Chang MN, et al. Characterization of a plateletactivating factor receptor antagonist isolated from haifenteng (piper futokedsura): specific inhibition of in vitro and in vivo plateletactivating factor induced effects. Pro Natl Acad Sci USA, 1985; 82(3)∶672. |
7. | Kobayashi H, Nonami T, Kurokawa T, et al. Mechanism and prevention of ischemiareperfusion induced liver injury in rats. J Surg Res, 1991; 51(1)∶240. |
8. | Born GVR. Aggregation of blood platelets by adenosine diphosphate and it’s reversal. Nature, 1962; 194(4832)∶927. |
9. | Whittle BJR, BoughtonSmith NK, Hutcheson IR, et al. Increased intestinal formation of PAF in endotoxininduced damage in the rat. Br J Pharmac, 1987; 92(1)∶3. |
10. | Ontell SJ. Pharmacologic modulation of experimental postischemic hepatic function. Ann Surg, 1989; 209(2)∶200. |
11. | Jaeschk H. Neutophils and kupffer cell induced oxidant stress and IR injury in the rat liver. Am J Physiol, 1991; 260(3)∶G335. |
12. | 陳清,冬利家,蘇靜怡等.血小板激活因子在小腸缺血再灌注損傷中的意義及山莨菪堿的保護作用.基礎醫(yī)學與臨床, 1993; 13(4)∶56. |
13. | Ludwig JC, McManus LM, Clark PO, et al. Modulation of plateletactivating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMNs)∶ role of extracellular Ca2+. Arch Biochem Biophys, 1984; 232(1)∶102. |
14. | Kochanek PM, Dntka AJ, Kumaroo KK, et al. Plateletactivating factor receptor blockers enhances recovery after mutifocal brain ischemia. Life Science, 1987; 41(24)∶2639. |
- 1. McCord JM. Oxygenderived free redicals in post ischemic tissue injury. New Engl J Med, 1985; 312(3)∶159.
- 2. Kane AB, Young EE, Schanne FAX, et al. Calcium dependence of phalloidininduced liver cell death. Proc Natl Acad Sci USA, 1980; 77(2)∶1177.
- 3. Braquet P, Koltai M, Bourgain R, et al. Is there a care for PAF antagonists in the treatment of ischemic states? TIPs, 1989; 10(1)∶23.
- 4. Gardner CR, Laskin JD, Laskin DL. Plateletactivatingfactor induced calcium mobilization and oxiditive metabolism in hepatic macrophagesand endothelial cells. J Leukoc Biol, 1993; 53(1)∶190.
- 5. Jaeschke H, Farhood A, Smith CW. Neutrophils contribute to ischemia/reperfusion injury in rat liver invivo. FASEB J, 1990; 4(A120)∶3353.
- 6. Shen TY, Hwang SB, Chang MN, et al. Characterization of a plateletactivating factor receptor antagonist isolated from haifenteng (piper futokedsura): specific inhibition of in vitro and in vivo plateletactivating factor induced effects. Pro Natl Acad Sci USA, 1985; 82(3)∶672.
- 7. Kobayashi H, Nonami T, Kurokawa T, et al. Mechanism and prevention of ischemiareperfusion induced liver injury in rats. J Surg Res, 1991; 51(1)∶240.
- 8. Born GVR. Aggregation of blood platelets by adenosine diphosphate and it’s reversal. Nature, 1962; 194(4832)∶927.
- 9. Whittle BJR, BoughtonSmith NK, Hutcheson IR, et al. Increased intestinal formation of PAF in endotoxininduced damage in the rat. Br J Pharmac, 1987; 92(1)∶3.
- 10. Ontell SJ. Pharmacologic modulation of experimental postischemic hepatic function. Ann Surg, 1989; 209(2)∶200.
- 11. Jaeschk H. Neutophils and kupffer cell induced oxidant stress and IR injury in the rat liver. Am J Physiol, 1991; 260(3)∶G335.
- 12. 陳清,冬利家,蘇靜怡等.血小板激活因子在小腸缺血再灌注損傷中的意義及山莨菪堿的保護作用.基礎醫(yī)學與臨床, 1993; 13(4)∶56.
- 13. Ludwig JC, McManus LM, Clark PO, et al. Modulation of plateletactivating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMNs)∶ role of extracellular Ca2+. Arch Biochem Biophys, 1984; 232(1)∶102.
- 14. Kochanek PM, Dntka AJ, Kumaroo KK, et al. Plateletactivating factor receptor blockers enhances recovery after mutifocal brain ischemia. Life Science, 1987; 41(24)∶2639.