白介素-2诱发低血压动物的实验研究

Experimental Studies on Interleukin-2-inducedHypotension in Rats

白介素－２（ＩＬ－２）广泛用于治疗恶性肿瘤，由于大剂量可引起严重的低血压且机制不明，限制了其大剂量的使用。本研究用国产重组人白介素－２（ｒｈＩＬ－２）复制大鼠低血压模型并探讨其机制。２４只ｗｉｓｔａｒ大鼠随机分成３组（每组ｎ＝８）：正常对照组，ＩＬ－２实验组（ｒｈＩＬ－２）和氨基胍（ＡＧ）治疗组。结果显示：（１）ＩＬ－２可使大鼠提睾肌微动脉扩张及ＭＡＰ下降，肺、肾、肝组织Ｅｖａｎ′ｓＢｌｕｅ含量明显增加。（２）ＡＧ可使ｒｈＩＬ－２引起的低血压回升及微动脉缩小，肺组织Ｅｖａｎ′ｓＢｌｕｅ含量明显下降。提示：ｒｈＩＬ－２引起低血压，可能与ＩＬ－２诱导ＮＯ产生，使血管扩张及通透性增加有关。

? It was reported that hypotension induced by IL-2 in cancer therapy was associated with vascular leak syndrome.(VLS) or vascular dilatation mediated by nitric oxide (NO).This study aimed at investigating whether recombinant human IL-2(rhIL-2)could induce hypotension in rats and whether both VLS and NO were involved in hypotension induced by rhIL-2.24 wistar rats were randomly divided into 3 groups (1) control (NS),(2)rhIL-2,(3)rhIL-2 pluse aminoquanidine (AG).The results showed that:(1)In contrast to the control group,the arterioles were also dilated and MAP decreased significantly in rhIL-2 group.The content of Evan′s Blue was greatly increased in the tissue of lung,kidney and liver in rats at 180min.(2)In contrast to rhIL-2 group,MAP and the arterioles diameter were significantly ameliorated in rhIL-2+AG group.The content of Evan′s Blue in the tissue of lung was significantly reduced.Conclusion:Hypotension induced by rhIL-2 is attributed to both the dilatation of the arterioles and the increment of the vascular permeability and its mechanism may be related to the increment of inducible nitric oxide synthesis.