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2022, Vol. 26 ›› Issue (2): 205-210Ligustrazine furoxan complex protects against renal ischemia-reperfusion injury in miceLi Wanhai1, Dong Yuhang2, Shi Chao1, Jiang Yiyao1, 3, Liu Ge1, Diao Wenjie1, Wu Zhen1
Abstract: BACKGROUND: Ligustrazine and nitric oxide can both reduce acute kidney injury caused by renal ischemia-reperfusion. Our team synthesized a compound of ligustrazine furoxan (605-1) which can be degraded into ligustrazine monomer and nitric oxide in animals. This compound has therapeutic and preventive effects against ischemia-reperfusion injury. OBJECTIVE: To observe the therapeutic and preventive effects of 605-1 against acute renal ischemia-reperfusion injury in mice, and to explore its mechanism. METHODS: Forty-eight male C57 mice were randomly divided into six groups: sham operation group, model group (ischemia-reperfusion group), single administration group (605-1, 30 mg/kg), low, medium and high dose groups (ischemia-reperfusion+10, 20, 30 mg/kg 605-1, respectively). Mice in the sham operation group and the single administration group underwent sham operation without renal ischemia treatment, and those in the model group and the three administration groups were used to make acute kidney injury models caused by renal ischemia-reperfusion. Pre-treatments in each group were conducted at 24 and 2 hours before operation. Normal saline was intraperitoneally given in the sham operation and model groups. After 24 hours of ischemia-reperfusion, the levels of serum creatinine and urea nitrogen and the pathological changes of renal tissue were measured. The expression of kidney injury molecule 1, Nox4, p65, and P-p65 was detected at the protein level. The expression of kidney injury molecule 1, tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 were detected at the RNA level. All animal experiment procedures were approved by the Animal Ethics Committee of Anhui Medical University. RESULTS AND CONCLUSION: The single administration group (30 mg/kg) had no renal toxicity. Compared with the model group, in the low, medium and high dose groups, histomathological examinations of the renal tissue showed pathological renal tubule dilation and brush border loss, tubular cell loss was significantly reduced, serum creatinine and urea nitrogen levels were significantly reduced; the protein and mRNA levels of kidney injury molecule 1 in renal tissue also decreased significantly, and immunohistochemical examination showed that the distribution and quantity of kidney injury molecule 1 expression in renal tissue decreased significantly; the protein levels of Nox4, p65, and P-p65 were down-regulated; the mRNA levels of tumor necrosis factor-α, interleukin-6 and monocyte chemoattractant protein 1 were significantly reduced. To conclude, 605-1 has a preventive effect against renal ischemia-reperfusion injury in mice, and its mechanism is related to anti-oxidative stress and inhibition of inflammation. Key words:ligustrazine furoxan complex, renal ischemia-reperfusion injury, acute kidney injury, oxidative stress, inflammatory reaction |