磷脂酶A2诱导物反义寡核苷酸靶向脂质体的抗损伤效应

Sever trauma,infection and shock caused systemic inflammatory response syndrome (SIRS)are main reasons of mutiple organ dysfunction syndrome(MODS).The later become the three death factors at peace times.PhospholipaseA2(PLA2) is consider as the center point of infection ischemia/reperfusion and shock though its over activation. Preventing of PLA2 over activation after server trauma is the key point of controlling systemic SIRS. This work attend to specficly block PLA2 activity by its antisense nucleotides carrying by immunoliposome and ph sensitive liposome. By this way, we can offer theory and experimental techniquce for server trauma,infection and shock and reduce side effects.By the support of this foundation, two kinds of impotant cytokin RIA methods were estamblished, which is IL-1 and IL-1ra and believed to be very closed with immflamation response. Otherwise, we also have cloned and recombinaed lipocortin-1, one kind of endogenal antagist protein to PLA2.This protein also has been purified and identyed for the furher research related with PLA2 activity. At the same time, we have made ph sensitive liposome for carrying PLA2 antisese nucleotides into cells to observe the effect of LPS induced IL-1 and IL-6 releases. We find that those ph sensitive liposome is enriched in important organs after intestinal ischemia/reperfusion injuries, which indicated that this kind of liposome can be used to carry PLA2 blocker and some other gene antagonists. This resuls is one good base for the research work of PLA2 RNAi .Under the support of this foundatin, we have get the good results in PLA2 activity and IL-1 or IL-1ra after server trauma and infection. Results show that PLA2 may be mediated the secreting and releaseing in systemic inflammatory responses .The injury may be reduced by blocking the PLA2 activity, which may be mainly is 85 kd subtype of PLA in cell.

体外多因素激活单核巨噬细胞，通过差异显示PCR获得磷脂酶A2激活介导的差异DNA。分析该序列并合成反义寡核苷酸。奖磷脂酶A2和白介素8抗体偶联于脂南体后包载反义寡核苷酸，僮镜ズ司奘上赴蜃⑷氤θ毖俟嘧⑺鹕舜笫螅ü鄄煜赴翁置诠δ芗岸运鹕说谋；ぷ饔茫教至字窤2激活诱导的基因在严重创伤后失控炎症反应中的信号传导机理。....