ischemic reperfusion
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2022 ◽  
Vol 12 ◽  
Ping Huang ◽  
Haitong Wan ◽  
Chongyu Shao ◽  
Chang Li ◽  
Ling Zhang ◽  

Cerebral ischemic reperfusion injury (CI/RI) is a critical factor that leads to a poor prognosis in patients with ischemic stroke. It is an extremely complicated pathological process that is clinically characterized by high rates of disability and mortality. Current available treatments for CI/RI, including mechanical and drug therapies, are often accompanied by significant side effects. Therefore, it is necessary to discovery new strategies for treating CI/RI. Many studies confirm that Chinese herbal medicine (CHM) was used as a potential drug for treatment of CI/RI with the advantages of abundant resources, good efficacy, and few side effects. In this paper, we investigate the latest drug discoveries and advancements on CI/RI, make an overview of relevant CHM, and systematically summarize the pathophysiology of CI/RI. In addition, the protective effect and mechanism of related CHM, which includes extraction of single CHM and CHM formulation and preparation, are discussed. Moreover, an outline of the limitations of CHM and the challenges we faced are also presented. This review will be helpful for researchers further propelling the advancement of drugs and supplying more knowledge to support the application of previous discoveries in clinical drug applications against CI/RI.

2022 ◽  
Vol 12 ◽  
Shuang Wu ◽  
Chengwei Liang ◽  
Xiaoyun Xie ◽  
Haiping Huang ◽  
Jinfeng Fu ◽  

Ischemic stroke is a major type of stroke worldwide currently without effective treatment, although antiplatelet therapy is an existing option for it. In previous studies, heat shock protein 47 (Hsp47) was found to be expressed on the surface of human and mice platelets and to strengthen the interaction between platelets and collagen. In recent years, Col003 was discovered to inhibit the interaction of Hsp47 with collagen. We evaluated whether the Hsp47 inhibitor Col003 is a promising therapeutic agent for ischemic stroke. Here, we first verified that Hsp47 is also expressed on the surface of rat platelets, and its inhibitor Col003 significantly inhibited thrombus formation in the FeCl3-induced rat carotid arterial thrombus model. Both Col003 and clopidogrel did not alter the bleeding time or coagulation parameters, while aspirin increased the tail-bleeding time (p < 0.05). The low cytotoxicity level of Col003 to rat platelets and human liver cells was similar to those of aspirin and clopidogrel. Col003 inhibited collagen-induced platelet aggregation, adhesion, [Ca2+]i mobilization, P-selectin expression, reactive oxygen species production and the downstream signal pathway of collagen receptors. The results of the middle cerebral artery occlusion model indicated that Col003 has a protective effect against cerebral ischemic–reperfusion injury in rats. The Hsp47 inhibitor Col003 exerted antiplatelet effect and protective effect against brain damage induced by ischemic stroke through the inhibition of glycoprotein VI (GPVI)and mitogen-activated protein kinase (MAPK) signaling events, which might yield a new antiplatelet agent and strategy to treat ischemic stroke.

Diabetes ◽  
2021 ◽  
pp. db210322
Han Feng ◽  
Hao Shen ◽  
Matthew J Robeson ◽  
Yue-Han Wu ◽  
Wu Hong-Kun ◽  

2021 ◽  
Vol 23 (5) ◽  
pp. 1089-1104
Yu. Yu. Borschev ◽  
I. Yu. Burovenko ◽  
A. B. Karaseva ◽  
S. M. Minasyan ◽  
E. S. Protsak ◽  

Overweight and obesity are among the main factors of cardiovascular risk, but the prospective studies on the dependence between high-fat diets and weight gain yielded contradictory results. Different types of fats exert varying metabolic effects, and this fact leads to a difference in the risk associated with increasing body weight. The effects of fat quality in the daily diet on immunological status and resistance of myocardium to ischemic-reperfusion damage should be studied experimentally in biomedical models. The purpose of this work was to assess the effect of the qualitative composition of a high-fat diet used for induction of primary visceral obesity (PVO) in rats with systemic inflammatory response syndrome (SIRS) upon myocardial resistance to ischemic-reperfusion injury, and levels of pro- and anti-inflammatory cytokines.The experiments were performed on adult male Wistar rats with PVO caused by 28-day consumption of any fat types: hydrogenated fats (HF), vegetable oils (VO), animal fats (AF) or milk fat (MF). The SIRS model included a combination of chemically induced colitis (CIC) and intragastric injection of a broad-spectrum antimicrobial agent (AMA) for three days. Five days later, immunological and biochemical studies were conducted, as well as composition of intestinal microbiota in faecal samples, morphological changes in the structure of the large intestine, hemodynamic parameters and myocardial resistance to ischemic-reperfusion injury were studied in the model of isolated heart perfusion, by Langendorff technique.There was a significant increase in the concentration of anti-inflammatory cytokines in animals with SIRS, i.e., TNFα, IL-1α, IL-2, IL-8, as well as a decrease in TGF-1β, an anti-inflammatory cytokine. SIRS was accompanied by severe dietary disorders and evacuatory function of the gastrointestinal tract. Minimal changes in the intestinal microbiota composition, as well as the most pronounced regeneration signs of intestinal epithelium was observed in rats in the group with MF injection. There was a trend for increasing size of infarction in all the groups as compared with control, directly correlating with increase in BDNF and IL-2 production. However, a significant increase in the infarction size was found only in the group receiving milkfat, thus suggesting a decrease in myocardial resistance to ischemic reperfusion injury (IRI).Thus, the presence of SIRS in the primary obesity model is characterized by controllable change of inflammation markers and depends on the quality of dietary fats. The degree of morphofunctional deterioration of isolated heart, including a decrease in resistance to ischemia-reperfusion injury, correlates with the concentration of BDNF and IL-2 during the studied observation terms.

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