Abstract
Cell necrosis and neuroinflammation play an important role in brain injury induced by ischemic stroke. Previous studies reported that Taohong Siwu decoction (THSWD)can reduce heart muscle cell necrosis and has anti-inflammatory properties. In this study, we investigated the effects of THSWD on cell necrosis and neuroinflammation in a rat model of middle cerebral artery occlusion (MCAO). Thirty-six male Sprague-Dawley (SD) rats were randomly divided into three groups with 12 rats in each group. They were the sham operation group, MCAO model group, and MCAO + THSWD group. We used ELISA to determine the levels of TNF-α, Mcp-1, and IL-1β inflammatory factors in rat serum, qRT‐PCR to detect the expression of TNF‐α, Mcp‐1 and IL‐1β mRNA in rat brain, and immunohistochemistry to detect the number of microglia and neutrophils in rat brain. qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of IBA-1 and MPO inflammatory factors and the TNF-α/RIP1/RIP3/MLKL pathway in the rat brain and protein expression levels. Compared with the sham operation group, the expression of MCP-1, IL-1β, IBA-1, and MPO inflammatory factors and the TNF-α/RIP1/RIP3/MLKL pathway were significantly upregulated in the MCAO group. Compared with the MCAO group, the expressions of MCP-1, IL-1β, IBA-1, and MPO inflammatory factors and the TNF-α/RIP1/RIP3/MLKL pathway were significantly downregulated in the MCAO + THSWD group. THSWD can reduce the expression levels of MCP-1, IL-1β, IBA-1, and MPO inflammatory factors as well as the TNF-α/RIP1/RIP3/MLKL pathway. Meanwhile, it can reduce the necrosis and inflammation of brain cells after cerebral ischemia, so as to protect the brain tissue of rats.
Highlights
Ischemic stroke is a disorder of cerebral blood circulation, which causes cerebral ischemia and hypoxia and leads to localized ischemic necrosis of brain tissue
By replicating the rat model of cerebral ischemia, this study explored whether Taohong Siwu decoction (THSWD) can reduce cell necrosis and neuroinflammation in the rat model of middle cerebral artery occlusion (MCAO) by inhibiting the expression levels of MCP-1, IL-1β, IBA-1, and MPO inflammatory factors as well as the tumor necrosis factor-α (TNF-α)/RIP1/RIP3/mixed lineage kinasedomain-like protein (MLKL) pathway
The qPCR results showed that the mRNA expressions of IBA-1 and MPO significantly increased in the MCAO group compared with the sham operation group (p < 0.01); compared with MCAO group, the mRNA expression of THSWD group decreased significantly (p < 0.05), as shown in Figures 5, 6
Summary
Ischemic stroke is a disorder of cerebral blood circulation, which causes cerebral ischemia and hypoxia and leads to localized ischemic necrosis of brain tissue. It can activate nonspecific inflammation of local tissue, which is an important factor for aggravating ischemic brain injury. Cell necrosis and neuroinflammation play an important role in transient ischemic stroke and reperfusion (Chen et al, 2016; Wang et al, 2021). Cell Necrosis and Neuroinflammation in MCAO infiltrating neutrophils and activated microglia produce free radicals and oxidants that damage central nervous system tissues, which lead to long-term disability and death in stroke patients (Roger et al, 2012). The development of a protective strategy against cell necrosis and neuroinflammation may be an effective approach in the treatment of patients with ischemic stroke
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