乌司他丁与内质网分子伴侣免疫球蛋白结合蛋白的分子对接和结合作用

目的 通过测定乌司他丁与免疫球蛋白结合蛋白（Bip）在脑缺血再灌注模型大鼠血清、大脑皮层中的浓度，以及两者的体外结合实验、模拟分子对接模型，探讨两者之间的相互作用。方法将36只雄性SD大鼠随机分为两组。正常组(n=18)大鼠经静脉注射乌司他丁20万IU/kg作为对照。实验组(n=18)大鼠在建立大脑中动脉栓塞模型（MCAO）后随即静脉注射乌司他丁20万IU/kg。采用酶标仪法、ELISA法分别测定乌司他丁及Bip在大鼠脑缺血后05、3、24 h中血清、大脑皮层中的浓度。通过乌司他丁与Bip的结合实验计算两者结合率，并利用软件模拟乌司他丁与Bip的分子对接模型。结果在患侧大脑皮层中，实验组乌司他丁浓度在3 h升高，24 h下降，而Bip浓度则在3 h中下降，24 h升高。乌司他丁与Bip的结合率为44%～62%，分子对接结果显示乌司他丁与Bip中的残基可形成范德华力及共轭作用，两者可形成不稳定复合物。结论在缺血大脑皮质中乌司他丁可与Bip形成不稳定复合物，其可能通过影响Bip的表达而在脑缺血再灌注中发挥着一定作用。

Molecular docking and combined effect between ulinastafin and endoplasmic reticulum chaperones immunoglobulin binding protein

Objective To investigate the interaction between ulinastatin and endoplasmic reticulum chaperones binding immunoglobulin protein (Bip), by assessing their concentration in cerebral ischemia reperfusion rats′ serum and cerebral cortex. Methods Thirty-six male SD rats were randomly divided into 2 groups, control group and experimental group. Rats in control groups (n=18) were intravenously treated with 200 000 IU/kg ulinastatin, while experimental group were intravenously injected with 200 000 IU/kg ulinastatin immediately after middle cerebral artery embolism (MCAO) (n=18, MCAO group). The concentration of ulinastatin and Bip in serum and cerebral cortex were measured by enzyme-labeled instrument and ELISA, 05 h, 3 h and 24 h after rat cerebral ischemia. The binding rate of ulinastatin and Bip was calculated by the combined test, and the molecular docking of ulinastatin and Bip was simulated by software. Results In ipsilateral side of afftected cerebral cortex, the concentration of ulinastatin was increased at 3 h and reduced at 24 h in MCAO group, while the concentration of Bip decreased at 3 h and increased at 24 h. The binding rate of ulinastatin and Bip was 44%-62%. Molecular docking showed that ulinastatin and Bip residues can form van der Waals force, conjugation effect and unstable complex. Conclusion Ulinastatin is able to combine with Bip, their unstable complex may play a role in cerebral ischemia disease.