| Objective To observe the clinical efficacy of ginkgolide in the treatment of ischaemic stroke and to investigate its mechanism for improving the prognosis of cerebral ischaemia-reperfusion injury in rats. Methods In clinical studies, 60 patients with ischemic stroke were collected from the Inpatient Department of the North District of the First Affiliated Hospital of Anhui Medical University from January 2022 to September 2023. They were divided into an observation group and a control group according to the random number table method, with 30 cases in each group.The control group routinely used antiplatelet drugs, lipid regulation and stabilisation of plaque, blood pressure lowering and neurological function protection drugs, and the observation group received combined infection with ginkgolide injection on this basis for a period of 10 days. Neurological function (NIHSS) scores, clinical efficacy, ability to perform activities of daily living (Barthel) scores, and gene and protein expression levels of Kelch-like echassociated protein 1(Keap1) and nuclear factor erythroid 2 related factor2(Nrf2) in peripheral blood mononuclear cells (PBMCs) were compared between the two groups before and after treatment. In animal experiments, the ZeaLonga suture method was used to establish a rat cerebral ischemia model, in which there were 10 rats in each of the sham-operated group (NC group), the model group, and the ginkgolide group. Zea-Longa score was used to evaluate the degree of neurological injury in each group. The pathological changes of brain tissue were detected by HE staining, the percentage of cerebral infarction volume was detected by TTC staining, and the levels of interleukin (IL-2), IL-6 and tumor necrosis factor-α (TNF-α) in brain tissue and serum were detected by ELISA. The expression levels of Keap1 and Nrf2 gene and protein in brain tissue and PBMC were detected by Real-time PCR and Western blot, respectively. Results In the clinical study, the total effective rate of the observation group (93.33%) was higher than that of the control group (70.00%) (P< 0.05). Compared with the control group after treatment, the NIHSS score of the observation group was significantly lower (P<0.05), the Barthel Index score was significantly higher (P<0.01), the Keap1 protein expression level was significantly down-regulated (P<0.01), and the Nrf2 mRNA and protein levels were significantly up-regulated after treatment(P<0.01) .In the animal experiment, compared with the model group, the neural function score of ginkgolide group was significantly reduced(P< 0.01). The pathological status of brain tissue in rats was improved significantly. The volume of cerebral infarction was significantly decreased (P＞0.05). The expressions of inflammatory factors TNF- α, IL-2 and IL-6 in brain homogenate and serum were significantly down-regulated (P< 0.01). Keap1 mRNA and protein expression levels in brain tissue and PBMC were significantly down-regulated (P＜0.01), while Nrf2 mRNA and protein expression levels were significantly up-regulated (P< 0.01). Conclusions Ginkgolide may inhibit oxidative stress and inflammatory response through the Keap1/Nrf2 signaling pathway, thereby improving stroke blood-brain barrier function, reducing brain injury, and enhancing neurological function. |
