RESUMO
The present study aimed to investigate the effects of sevoflurane postconditioning in a rat brain cerebral ischemiareperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Tolllike receptor4 (TLR4) inhibitor group (Tak242), nuclear factor (NF)κB inhibitor group (QNZ) and Sevoflurane postconditioning combined with TLR4NFκB signaling pathway inhibitor group (Se + Tak242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4NFκB signaling pathway were assayed by western blot analysis. Sevoflurane postconditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin1, Bad and CleavedCaspase3 proteins were inhibited and the expression of Bcl2 protein was upregulated after sevoflurane administration. Sevoflurane postconditioning also inhibited the TLR4 protein and NFκB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak242 and QNZ groups were not significantly different compared with the Se group (P>0.05), and the Se + Tak242 group had the best results. The present study demonstrated that sevoflurane postconditioning could protect middle cerebral artery occlusioninduced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4NFκB signaling pathway.
Assuntos
Apoptose/efeitos dos fármacos , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Sevoflurano/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Masculino , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
The present prospective, randomized, double-blinded, controlled study aimed to investigate the efficacy and safety of dexmedetomidine (DEX) combined with butorphanol for patient-controlled intravenous analgesia (PCIA) following total laparoscopic hysterectomy. A total of 88 patients undergoing total laparoscopic hysterectomy and receiving postoperative PCIA were divided into two groups following surgery. Patients received DEX 0.5 µg/kg intravenously in the DEX group or 0.9% normal saline in the control (CON) group following anesthesia induction. Postoperatively, the PCIA (10 mg butorphanol with 300 µg dexmedetomidine in the DEX group or without DEX in the CON group) was delivered as a 0.5 ml bolus (lockout interval of 15 min) with a continuous background infusion of 2 ml/h. Cardiovascular and respiratory variables, cumulative butorphanol consumption, pain scores, level of sedation, concerning adverse events and the degree of patient satisfaction were recorded for 24 h post-surgery. A total of 81 patients completed the study. Blood pressure and heart rate exhibited no significant difference between the two groups during surgery and for 24 h post-surgery. Compared with the CON group, patients in the DEX group required ~19% less butorphanol (P<0.05). During the first 24 h post-surgery, patients from the DEX group had a significantly lower visual analogue scale score at rest and movement states compared with the CON group (P<0.05). There was no significant difference in sedation score between the groups. The satisfaction scores were significantly higher in the DEX group compared with those in the CON group (P<0.05). Compared with the CON group, the DEX group exhibited a lower rate of postoperative nausea and vomiting (P<0.05). There was no occurrence of serious adverse events, including respiratory depression, hypotension, bradycardia and somnolence. In conclusion, following total laparoscopic hysterectomy, the loading dose of DEX (0.5 µg/kg) followed by a continuous infusion as an adjunct to butorphanol PCIA resulted in effective analgesia, significant butorphanol sparing and less butorphanol-induced nausea and vomiting without excessive sedation or adverse effects. The trial registration number was ChiCTR1800015675 at the Chinese Clinical Trial Registry (chictr.org.cn) and the date of registration was 4th April 2018.