Deng Yi, Li Rachel W, Yang Yong Liang, Weiss Steven, Smith Paul N
Medical School, Australian National University, Canberra, Australian Capital Territory, Australia.
Department of Orthopaedic Surgery, Canberra Hospital, Yamba Drive, Garran, Australian Capital Territory, Australia.
ANZ J Surg. 2022 Mar;92(3):518-525. doi: 10.1111/ans.17381. Epub 2021 Nov 24.
Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti-ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model.
Winstar rats (n = 48) were divided into four groups (n = 12 per group)-three treatment groups and one control group. Riluzole, Lidocaine and Lamotrigine were given prior to renal ischemia only (IO) or IRI. The degree of ischemia was measured by glutathione levels and a TUNEL assay was used to measure DNA fragmentation.
Riluzole, Lidocaine and Lamotrigine pre-treatment each resulted in statistically higher glutathione levels compared to controls (P = 0.002; P = 0.007 and P = 0.005, respectively). Riluzole and Lidocaine were also effective at preventing depletion of glutathione following IO (P = 0.007 and P = 0.014 respectively), while Lamotrigine was ineffective in IO (P = 0.71). The degree of DNA fragmentation seen on the TUNEL assay was markedly reduced in all three-drug groups in both IO and IRI.
Riluzole, Lidocaine and Lamotrigine all have anti-ischaemic effects in the rat kidney and can have potential therapeutic implications.
肾缺血再灌注损伤（IRI）可导致严重的发病率和死亡率。它仍然是急性肾损伤的主要原因，因此是创伤和肾移植手术中的一个重要问题。人们尝试使用各种药物来减轻IRI的有害影响，但很少有药物在临床上被证明是有效的。利鲁唑、利多卡因和拉莫三嗪已被证明在其他器官中具有抗缺血特性；然而，它们在肾脏中的应用尚未得到测试。我们使用大鼠模型研究了利鲁唑、利多卡因和拉莫三嗪对肾IRI的预防作用。
将Wistar大鼠（n = 48）分为四组（每组n = 12）——三个治疗组和一个对照组。仅在肾缺血（IO）或IRI之前给予利鲁唑、利多卡因和拉莫三嗪。通过谷胱甘肽水平测量缺血程度，并使用TUNEL测定法测量DNA片段化。
与对照组相比，利鲁唑、利多卡因和拉莫三嗪预处理后的谷胱甘肽水平在统计学上均显著更高（分别为P = 0.002；P = 0.007和P = 0.005）。利鲁唑和利多卡因在预防IO后谷胱甘肽的消耗方面也有效（分别为P = 0.007和P = 0.014），而拉莫三嗪在IO中无效（P = 0.71）。在IO和IRI中，所有三个药物组在TUNEL测定中观察到的DNA片段化程度均显著降低。
利鲁唑、利多卡因和拉莫三嗪在大鼠肾脏中均具有抗缺血作用，并可能具有潜在的治疗意义。
