钙超载和血小板激活因子对肺组织释放降钙素墓因相关肽的影响

EFFECT OF CALCIUM OVERLOAD AND PLATELET ACTIVATING FACTOR ON CALCITONIN GENE RELATED PEPTIDE RELEASE FROM LUNG TISSUE

在肠缺血／再灌注（I／R）损伤的大鼠模型中，用放射免疫法分析血浆和离体肺灌洗液中降钙素基因相关肽（CGRP）。结果发现I／R损伤后血浆CGRP水平较自身伤前增高161．3％（P＜0．01），伤前预先用血小板激活因子受体阻断剂（SR27417A），血浆CGRP仍然高于自身伤前117．8％（P＜0．01）。而假手术组没有明显变化。另外，I／R损伤组大鼠离休肺灌洗液同正常对照相比，CGRP还下降17．4％，而SR27417A用药组离体肺CGRP比正常对照增高97．9％。在进一步离体实验中发现，钙离子载体A23187和血小板激活因子（PAF）促进离体大鼠肺组织释放CGRP，磷脂酶A2阻断剂4-溴苯甲酰溴甲烷（p-BPB）可以阻断A23187的这种作用，而SR27417A仅能阻断PAF的上述效应。用SR27417A预先灌流离体肺组织可将灌洗液中CGRP浓度提高144．6％，而后再用A23187灌流同一肺组织则比单纯用A23187灌流时低114．6％，比正常对照还低14．8％。同样，SR27417A预灌流后再用PAF灌流，则肺组织CGRP释放较单纯用PAF时低13．7％，但比正常对照仍高55．6％。以上结果提示：（1）I／R损伤后血浆中CGRP浓度显著升高而肺灌洗液中CGRP的变化不明显；（2）体外肺组织释放CGRP可能同胞内钙离子增加和磷脂酶A2激活及PAF合成增加相关；

The level of calcitonin gene related peptide(CGRP)in plasma and pulmonary lavage fluid was tested by radio-immunoassay on intestinal ischemia/reperfusion(I/R)injured rat.The results showed that plasma CGRP after I/R was 161.3% more than control,and 117.8% when pre-treated with platelet activating factor(PM)receptor antagonist SR27417A before injury but no obvious changes were observed in the sham group.Meanwhile,CGRP was reduced by 17.4% in pulmomary lavage fluid in I/R animal and elevated by 97.9% in SR27417A pre-treated animal,compared with normal control.Furthermore,it was demonstrated that CGRP release from lung tissue was enhanced concentration-dependeuly by calcium ionophores A23187 or PAF,as a result of blockage by phospholipase A2 inhibitor p-BPB or SR27417A respectively.In vitro experiment,CGRP in pulmonary lavage fluid was 144.6% more than control when pre treated with SR27417A and 114.6% less than that treated with A23187 only,even 14.8% less than control.Much the same,CGRP release was 13.7% less than that treated with PAF and was 55.6% more than control when pre-treated with SR27417A only.All these results indicated that(1)CGRP was significantly increased in plasma but without obvious changes in pulmonary lavage fluid following I/R injury;(2)lung tissue CGRP release may be related with Ca2+ increase in cells or phospholipase A2 activation as well as PAF increase;(3)SR27417A was a kind of strong reagent,which may promote CGRP release in vivo and in vitro,but block the effect of PAF on CGRP release.Supported by a grant from'95'Medical and Scientific Research Foundation of the Army(No.96LD53)