Department of Anesthesiology, Ningbo First Hospital, No. 59 Liuting Street, Haishu District, Ningbo, 315010, Zhejiang, China.
Mol Cell Biochem. 2020 Jan;464(1-2):73-81. doi: 10.1007/s11010-019-03650-4. Epub 2019 Nov 16.
Sepsis-associated acute kidney injury (AKI) is a life threatening condition with high morbidity and mortality. The pathogenesis of AKI is associated with apoptosis. In this study, we investigated the effects of ligustrazine (LGZ) on experimental sepsis-associated AKI in mice. Sepsis-associated AKI was induced in a mice model using cecal ligation and puncture (CLP) method. Mice were administered LGZ (10, 30, and 60 mg/kg) via tail vein injection 0.5 h before CLP surgery. Mice survival was evaluated. Renal water content was detected. Urine samples were collected for ELISA of Kim1. Kidneys were collected for nucleic acid analysis and histological examination. Pathological assessment was used to determine the effect of LGZ on sepsis-associated AKI. Caspase-3 expression in kidney was assessed by immunohistochemistry. Renal NMDAR1 level was also determined. Treatment of LGZ improved mice survival rate; the effect was significant when administered at a high LGZ dose (60 mg/kg). Renal water content of mice undergoing CLP was significantly reduced by LGZ treatment. Both middle-dose and high-dose LGZ treatments reduced urine Kim1 level in sepsis-associated AKI mice. The severity of AKI in septic mice was reduced by middle-dose and high-dose LGZ administration. Immunohistochemical analysis revealed decreased caspase-3 and NMDAR1 levels in the kidney following middle-dose and high-dose LGZ treatments. RT-PCR assay showed a significant reduction in NMDAR1 mRNA expression in the kidney of middle-dose and high-dose LGZ-treated mice. LGZ exhibited protective effects against sepsis-associated AKI in mice, possibly via downregulation of renal NMDAR1 expression and its anti-apoptotic action by inhibiting caspase-3.
脓毒症相关性急性肾损伤（AKI）是一种危及生命的疾病，具有高发病率和死亡率。AKI 的发病机制与细胞凋亡有关。在本研究中，我们研究了川芎嗪（LGZ）对实验性脓毒症相关性 AKI 小鼠的影响。使用盲肠结扎和穿孔（CLP）方法在小鼠模型中诱导脓毒症相关性 AKI。在 CLP 手术前 0.5 小时，通过尾静脉注射给予小鼠 LGZ（10、30 和 60mg/kg）。评估小鼠存活率。检测肾含水量。收集尿液样本进行 Kim1 ELISA。收集肾脏进行核酸分析和组织学检查。通过病理评估确定 LGZ 对脓毒症相关性 AKI 的影响。通过免疫组化评估肾脏中 caspase-3 的表达。还测定了肾脏 NMDAR1 水平。LGZ 治疗可提高小鼠存活率；高剂量 LGZ（60mg/kg）给药时效果显著。LGZ 治疗可显著降低 CLP 小鼠的肾含水量。中剂量和高剂量 LGZ 治疗均可降低脓毒症相关性 AKI 小鼠的尿 Kim1 水平。中剂量和高剂量 LGZ 给药可减轻脓毒症小鼠 AKI 的严重程度。免疫组化分析显示，中剂量和高剂量 LGZ 治疗后肾脏 caspase-3 和 NMDAR1 水平降低。RT-PCR 检测显示，中剂量和高剂量 LGZ 治疗小鼠肾脏中 NMDAR1 mRNA 表达显著降低。LGZ 对脓毒症相关性 AKI 具有保护作用，可能通过下调肾脏 NMDAR1 表达及其通过抑制 caspase-3 的抗凋亡作用。
