Research of the intracellular transmission mechanism of the information concerning stress response

PDE-III抑制剂米力农可抑制缺血再灌流期间肝组织中cAMP的降解。米力农可有效抑制再灌注期血清转氨酶的升高，其作用机制是改善血窦灌注率，减少白细胞与内皮细胞的相互作用。另一种PDE-III抑制剂Olprone和腺苷环化酶刺激剂NKH477也被检测。两者均能抑制再灌注期的转氨酶水平。奥普利通2号组ALT释放量为1725IU/L，为对照组的一半。然而，全身血压有下降到100毫米汞柱以下的趋势。NKH477对血压的影响较小，剂量在0.10~1.0r之间，0.2Gamma可使ALT降至1615IU/L，两者同时给药，ALT降至1434IU/L。虽然升高肝脏…的能力2伽玛奥普罗内的UE cAMP高于0.2伽马的NKH477，对ALT和血压的最终抑制作用提示NKH477比奥普罗内更适合临床使用。但仍需进一步研究。在应激反应过程中，核因子-kappaB是细胞内信息传递的重要分子之一。由于PDTC被认为可以抑制核因子-kappaB的激活，我们研究了PDTC对缺血再灌注损伤的影响。有趣的是，PDTC诱导了肝组织中的HO-1，并出现了显著的肝窦扩张，这可能是由于分子CO的增加所致。因此，PDTC可产生类似PDE-III抑制剂的肝脏缺血耐受。由于PDE-III抑制剂没有正弦扩张作用，因此PDE-III抑制剂和PDTC之间的信号转导似乎完全不同，尽管两者都是显著的耐受诱导剂。这些事实表明，与生物体对应激反应防御系统有关的分子信息具有复杂性和多样性。较少

A PDE-III inhibitor, Milrinone, could suppress cAMP degradation in the liver tissue during ischemia-reperfusion. Owing to this effect, serum transaminase increase during reperfusion was effectively suppressed by the Milrinone treatment.Concerning the mechanism for this beneficial effect, sinusoidal perfusion rate was improved and the leukocytes-endothelial interaction was significantly decreased. Another PDE-III inhibitor, Olprinone, and adenylate cyclase stimulator, NKH477, were also examined. Both of which could suppress the transaminase level during reperfusion. In Olprinone 2 gamma group, ALT release was 1725 IU/l. This value was as half as control. However, the systemic blood pressure was tended to decline below 100 mmHg. The effect of NKH477 on the blood pressure was mild with the dose between 0.1-1.0 gamma, and 0.2 gamma of NKH477 could suppress ALT to 1615 IU/l. When they were simultaneously administered, ALT decreased to 1434 IU/l. Although the power to increase the liver tiss … More ue cAMP was greater in 2 gamma Olprinone than 0.2 gamma NKH477, final effects on ALT suppression and blood pressure suggested that NKH477 is better for clinical use than Olprinone. However, further study is necessary.In the process of stress response, NF-kappaB is one of the most important molecules concerning intracellular information transmission. Since the PDTC is said to suppress the activation of NF-kappaB, we examined the effects of PDTC administration on ischemia-reperfusion injury. Interestingly, PDTC induced HO-1 in the liver tissue and developed remarkable sinusoidal dilatation, probably due to an increase of molecular CO. Consequently, PDTC could produce ischemic tolerance of the liver like PDE-III inhibitors. Since the PDE-III inhibitor had no sinusoidal dilatation effect, signal transduction seemed to be completely different between PDE-III inhibitor and PDTC, although both of which are significant tolerance inducer. These facts indicate the complexity and multiplicity of the molecular information relating to defense system of organism to the stress. Less