Objective. With the increasing incidence of diabetes mellitus (DM) combined with myocardial ischemia, how to reduce myocardial ischemia-reperfusion injury in DM patients has become a major problem faced by clinicians. We investigated the therapeutic effects of dexmedetomidine (DEX) on myocardial ischemia-reperfusion injury in DM rats and its effect on endoplasmic reticulum stress. Methods. SD rats with SPF grade were randomly divided into 6 groups: non-DM rats were divided into the sham operation group (NDM-S group), ischemia-reperfusion group (NDM-IR group), and dexmedetomidine group (NDM-DEX group); DM rats were divided into the diabetic sham operation group (DM-S group), diabetes-reperfusion group (DM-IR group), and diabetes-dexmedetomidine (DM-DEX) group, with 10 rats in each group. Then the effects of DEX on the changes of CK-MB and cTnT levels were examined. The effects of myocardial pathological damage and myocardial infarct size were detected. The apoptosis of cardiomyocytes was detected. The apoptosis of heart tissue cells was also tested through the expressions of cleaved caspase-3, Bcl-2, and Bax proteins. The expression of endoplasmic reticulum stress-related proteins GRP78, CHOP, ERO1α, ERO1β, and PDI was examined. The hypoxia/reoxygenation (H/R) injury cell model was established, the effects of DEX, DEX+ ERS agonist on cell apoptosis was also detected. Results. The myocardial damage of DM-IR was more severe than that of NDM-IR rats. DEX could reduce the expression of CK-MB and cTnT, reduce pathological damage, and reduce scar formation and improve fibrosis. DEX can reduce the expression of GRP78, CHOP, ERO1α, ERO1β, and PDI proteins in vivo and in vitro. And the effect of DEX on cell apoptosis could be blocked by ERS agonist. Conclusion. DEX attenuates myocardial ischemia-reperfusion injury in DM rats and H/R injury cell, which is associated with the reduction of ERS-induced cardiomyocyte apoptosis.

Di You, Lu Qin, Kai Li, Di Li, Guoqing Zhao, and Longyun Li. Korean J Pain 2021;34:271-87. https://doi.org/10.3344/kjp.2021.34.3.271

Background: Inhalation of sevoflurane can cause neuronal apoptosis, and cognitive disorders, inducing to the occurrence and progression of post operative cognitive dysfunction (POCD). This study aimed to explore the roles of sevoflurane-induced POCD-associated exosomes on HMC3 cells and its related mechanisms. Methods: Exosomes were isolated from the plasma of sevoflurane-induced POCD or non-POCD patients, and were then sent for small RNA sequencing. Real-time quantitative PCR (RT-qPCR) was used to verify the sequencing results, and miR-584-5p was chosen for subsequent study. HMC3 cells were respectively transfected with POCD-derived exosomes and miR-584-5p mimics, and cell viability and apoptosis were measured. Dual-luciferase reporter gene assay was applied to confirm the target of miR-584-5p. Results: After sequencing, 301 differentially expressed miRNAs were identified, including 184 up-regulated miRNAs and 117 down-regulated miRNAs, and were significantly enriched in 3577 GO terms and 121 KEGG pathways. Due to the high level of miR-584-5p in sevoflurane-treated POCD-derived exosomes, HMC3 cells with miR-584-5p enrichment were successfully established. Compared with the control group, POCD-derived exosomes and miR-584-5p significantly inhibited viability and promoted apoptosis of HMC3 cells (P < 0.05). The IL-1β and TNF-α levels were significantly increased after POCD-derived exosomes and miR-584-5p mimics treatment compared to the control group (P < 0.05). Besides, POCD-derived exosomes and miR-584-5p mimics significantly down-regulated the expression levels of BDNF and p-TrkB, and up-regulated Caspase 3 and IL-1β. Finally, BDNF was confirmed to be the target of miR-584-5p. Conclusions: Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p may regulate the growth of HMC3 cells via targeting BDNF.

Background: Present investigation evaluates the neuroprotective effect of Bletilla striata on isoflurane induced neuronal injury rat model. Methodology: Neuronal injury was induced by exposing the pups (P7) isoflurane (0.75%) in oxygen (30%) for the period of 6 hr and rats were treated with Bletilla striata at a dose of 35, 70 and 140 mg/kg, p.o. for the period of 21 days. At the end of protocol neurological score was estimated and serum concentration of inflammatory cytokines was estimated. Isolated brains tissue was prepared to perform immunohistochemical analysis, TUNEL assay and western blot assay. Results: Result of the study reveals that treatment with BS significantly (p<0.01) reduces the neurological score compared to negative control group. Level of inflammatory cytokines in the serum and the expression of p-Akt, Bcl-xL and Bad protein were significantly attenuated in BS treated group. Moreover the cleaved caspase-3 and TUNEL positive cell was significantly (p<0.01) reduced in BS treated group compared to negative control group of rats. Conclusion: Present study concludes that ethanolic extract of Bletilla striata protects the neuronal injury by reducing apoptosis in isoflurane induced neuronal injury rats.