Feng L, Xiong Y, Cheng F, Zhang L, Li S, Li Y
Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Transplant Proc. 2004 Sep;36(7):1949-51. doi: 10.1016/j.transproceed.2004.07.050.
Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice.
Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1.
I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01).
These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.
在尸体肾移植中，缺血再灌注（I/R）损伤是不可避免的。它会导致急性排斥反应和慢性移植物功能障碍。研究表明，川芎嗪是一种中药提纯的化学成分，是一种有效的血管收缩阻滞剂，具有很强的清除氧自由基的作用。由于热缺血再灌注可能比冷保存造成更大的损害，我们研究了川芎嗪对小鼠热缺血再灌注可能的保护作用。
对单侧肾切除的C57BL/6雄性小鼠进行50分钟的左肾缺血处理。第一组为假手术动物；第二组为未处理动物（生理盐水，缺血再灌注前30分钟腹腔注射）；第三组为川芎嗪处理动物（80mg/kg，缺血再灌注前30分钟腹腔注射）。再灌注24小时后处死小鼠。测定血清肌酐、血尿素氮、肾脏丙二醛（MDA）水平和超氧化物歧化酶（SOD），并用免疫组织化学法检测肾脏中Bcl-2和ICAM-1。
缺血再灌注使第二组小鼠肌酐和尿素氮水平增加了6倍。川芎嗪使增加量减半，并减轻了肾小管坏死和凋亡（P<0.01）。川芎嗪降低了MDA水平，改善了SOD活性下调。缺血再灌注后Bcl-2上调，尤其是在川芎嗪处理组（P<0.01）。川芎嗪大大降低了ICAM-1的上调（P<0.01）。
这些发现表明，川芎嗪可减轻与肾脏热缺血再灌注相关的肾功能障碍。
