供受者围手术期应用乌司他丁对移植肾功能保护机制的探讨

Effects of applying ulinastatin in donors and recipients on the renal function of recipients in the living donor renal transplantation and the mechanism of renal protection

目的研究活体肾移植供受者围手术期应用乌司他丁（ulinastatin，UTI）对受者肾功能的影响，探讨其肾功能保护机制。方法将40对全身麻醉下活体肾移植供、受者按随机数字表法分为两组（每组20对）：UTI组（U组）和对照组（C组）。U组供者于阻断肾动脉前1h静脉泵注UTI5000U／kg（稀释至50ml，输注时间20min），受者于吻合肾血管开放后即刻泵注UTI5000U／kg（稀释至50ml，输注时间20min）；C组供、受者以同U组相同方案泵注等量生理盐水。两组受者在麻醉诱导前（T1）、吻合血管开放前15min（T2）、吻合血管开放即刻（T3）、手术结束时（T4）、术后6h（T5）、术后24h（T6）时的血浆血栓素A2（thromboxane A2，TXA2）、前列环素12（prostacyclin I2，PGI2）浓度[采用ELISA法检测T1-T6时待测血样中血栓素B2（thromboxane B2,TXB2）、6-酮-前列腺素F1α（6-ketone-prostaglandin F1α，6-keto-PGF1α）浓度（TXA2和PGI2在血浆中极不稳定，但通过测量两者的稳定代谢产物TXB2、6-keto-PGF1α可间接了解TXA2和PGI2的生成情况）及TXA2/PGI2比值和T1、T6、术后48h（T7）时的血肌酐（Serum creatinine，Scr）、半胱氨酸蛋白酶抑制剂C（cystatin C，Cys C）浓度及尿量。结果与T1时比较，两组受者T2～T6时血浆TXB2浓度均明显升高（P〈0．05），T4时达到峰值，之后降低，T6时仍高于术前水平；T2～T6时血浆6-keto-PGF1α浓度均升高（P〈0．05），T3时达到峰值，之后降低，T6时升高虽有统计学意义（P〈0．05），但基本恢复至术前水平；T2～T6两组TXB2，6-keto-PGF1α均明显升高（P〈0．05）；T6-T7时Scr及CysC水平明显降低（P〈0．05），尿量明显增多（P〈0．05）。与C组比较，U组T2～T6时血浆TXB2浓度明显降低（P〈0．05）；T4-T5时血浆6-keto-PGF1α浓度降低幅度明显下降（P〈0．05）；T2～T6时TXB拍-keto-PGF1α明显降低（P〈0．05）；T6～T7时Scr、CysC水平明显降低（P〈0．05）；T6～T7时虽尿量增多，但差异无统计学意义（P〉0．05）.结论UTI对TXA2/PGI2比例失衡有一定的调节作用，可通过此机制改善移植肾的血流灌注，对缺血／再灌注损伤（ischemia／reperfusion injury，I／RI）导致的移植肾功能受损有一定保护作用。

Objective To investigate the effects of ulinastatin（UT1）on renal function and the mechanism of renal protection, when using UTI in donors and recipients in living donor renal transplantation. Methods Forty pairs of patients were randomly assigned into two groups：the ulinastatin group （group U） and the control group （group C）. One hour before blocking renal artery, the donors in group U were given ulinastatin 500 U/kg （dissolved in 50 ml saline） for 20 min by intravenous pump, when the renal blood vessels opening,the recipients in group U were infused ulinastatin 500 U/kg （dissolved in 50 m] saline） for 20 min. The donors and recipients in group C received 50 ml saline solution in the same way. The serum thromboxane B2 （TXB2）, 6- ketone-prostaglandin F1α （6-keto-PGF1α） levels and the TXB2/6-keto-PGF1α were compared before anesthesia induction（T1）, 15 min before vessels opening（T2）, vessels opening immediately（T3）, the end of the operation（T4）, 6 h after surgery （T5）, 24 h after surgery （T6） in two groups： The serum creatinine （Scr） and cystatin C （CysC） levels were detected and urine volume was recorded at T1, T6 and 48 h after surgery （T7）.Results Compared with T1, the serum TXB2 levels in two group were significantly increased at the time points of T2-T6（P〈0.05）, while the serum TXB2 levels declined from their peaks of T4, the serum TXB2 levels still higher than before surgery , the serum 6-keto- PGF1α levels in these two groups were significantly increased at time points of T2-T6 （P〈0.05）. Although the serum 6-keto-PGF1α levels declined from their peak at T3, e their levels still higher than before surgery （P〈0.05）. The serum TXB2/6-keto-PGF1α level in two group were significantly increased at the points of T2-T6 （P〈0.05）. The serum creatinine and CysC levels in the two groups were significantly increased in T6 and T7 （P〈0.05）. Urine output remarkably increased in T6 and T7 （P〈0.05）. Compared with C, the serum TXB2 levels were significantly declined at the time points of T2-T6 （P〈0.05）, the serum 6-keto-PGF1α levels were distinctly recuced in T4 and T8（P〈0.05）, the serum TXB2/6-keto-PGF1α levels were dramatically decreased, the serum creatinine and cystatin C levels were significantly declined in T6 and T7 （P〈0.05）, urine output increased in T6 and T7, but there was no significant difference between these two groups （P〉0.05）. Conclusions UTI can protect renal function during related donor kidney transplantation, which is related to effectively correct the TXA2/PGI2 proportional unbalance to improve renal blood perfusion.