College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, PR China.
College of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, PR China.
Biomed Pharmacother. 2020 Nov;131:110723. doi: 10.1016/j.biopha.2020.110723. Epub 2020 Sep 26.
Stroke is an acute cerebrovascular disease caused by the sudden rupture of cerebral blood vessels or vascular obstruction from brain tissue damage or dysfunction, thereby preventing blood flow into the brain. Cerebral ischemia-reperfusion injury (CI/RI), a common syndrome of ischemic stroke, is a complex pathological process whose physiological mechanism is still unclear. Qishiwei Zhenzhu pills (QSW), a famous Tibetan medicine preparation, has the effect of tranquilizing by heavy settling, dredging channels and activating collaterals, harmonizing Qi and blood, restoring consciousness, and inducing resuscitation. Here, we investigated the protective effect of QSW on CI/RI in rats and its potential mechanism. First, the volatile and liposoluble components in QSW were determined using gas chromatography-mass spectrometry (GCMS). After 24 h of CI/RI, the neuroprotective effect was determined by evaluating the neurological function, cerebral infarction, histopathology, and blood-brain barrier (BBB) function. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blot (WB) were used to detect the expression of matrix metalloproteinase 9 (MMP-9), claudin-5, and occludin. Finally, GCMS metabonomics was used to identify different metabolites and analyze metabolic pathways. The results showed that 88 volatile components and 63 liposoluble components were detected in QSW. Following the experimental stroke operation, it was observed that rats administered QSW pretreatment had improved neurological function, reduced infarct volume (P < 0.01), increased Nissl bodies (P < 0.05), improved histopathology, and reduced BBB disruption. Immunofluorescence, RT-qPCR, and WB results showed that MMP-9 level in the brain tissue of the QSW pretreatment group had a decreasing trend and the expression of claudin-5 and occludin had a tendency to increase. Eleven metabolites related to lipid metabolism, fatty acid metabolism, and energy metabolism, were identified via GC-MS metabonomics. Our study shows that QSW preconditioning has a neuroprotective effect on CI/RI; however, its mechanism requires further study.
中风是一种由脑血管突然破裂或血管阻塞引起的急性脑血管疾病，导致脑组织损伤或功能障碍，从而阻止血液流入大脑。脑缺血再灌注损伤（CI/RI）是缺血性中风的常见综合征，是一种复杂的病理过程，其生理机制尚不清楚。奇士味珍珠丸（QSW）是一种著名的藏药制剂，具有重镇安神、通经活络、调和气血、醒脑开窍的功效。在这里，我们研究了 QSW 对大鼠 CI/RI 的保护作用及其潜在机制。首先，采用气相色谱-质谱联用（GCMS）法测定 QSW 的挥发性和脂溶性成分。在 CI/RI 后 24 小时，通过评估神经功能、脑梗死、组织病理学和血脑屏障（BBB）功能来确定神经保护作用。免疫荧光、实时定量 PCR（RT-qPCR）和蛋白质印迹（WB）用于检测基质金属蛋白酶 9（MMP-9）、闭合蛋白-5 和紧密连接蛋白的表达。最后，采用 GCMS 代谢组学鉴定不同的代谢物并分析代谢途径。结果表明，QSW 中检测到 88 种挥发性成分和 63 种脂溶性成分。经过实验性中风手术，观察到给予 QSW 预处理的大鼠神经功能改善，梗死体积减少（P < 0.01），尼氏小体增加（P < 0.05），组织病理学改善，BBB 破坏减少。免疫荧光、RT-qPCR 和 WB 结果表明，QSW 预处理组脑组织中 MMP-9 水平呈下降趋势，claudin-5 和 occludin 的表达呈上升趋势。通过 GC-MS 代谢组学鉴定出与脂质代谢、脂肪酸代谢和能量代谢相关的 11 种代谢物。我们的研究表明，QSW 预处理对 CI/RI 具有神经保护作用；然而，其机制需要进一步研究。
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