LncRNA OIP5-AS1 Mitigates Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Regulating NFAT5 Expression via Sponging miR-34b.

Bupivacaine (BUP), which is widely used in anesthesia, can cause neurotoxicity and neurological abnormalities. This work intended to study the function of long non-coding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) in BUP-triggered neurotoxicity. OIP5-AS1, microRNA (miR)-34b, and nuclear factor of activated T cells 5 (NFAT5) levels were examined via real-time quantitative PCR (RT-qPCR). Cell proliferation, caspase-3 activity, and apoptosis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), caspase-3 activity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The regulatory relationships between miR-34b and OIP5-AS1 or NFAT5 were validated via RNA binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Our data demonstrated that OIP5-AS1 and NFAT5 levels were downregulated and miR-34b was upregulated upon exposure to BUP. Functional assays implied that the OIP5-AS1 deficiency impeded cell proliferation and enhanced the apoptosis of DRG neurons, while OIP5-AS1 addition reversed these changes. Moreover, OIP5-AS1 could bind to miR-34b and OIP5-AS1 regulated BUP-induced neurotoxicity via miR-34b. Besides, miR-34b could directly interact with NFAT5. Augmentation of miR-34b impeded cell proliferation and expedited the apoptosis and caspase-3 activity, while NFAT5 addition neutralized these impacts. Finally, it was verified that OIP5-AS1 could upregulate NFAT5 through sponging miR-34b. In sum, our results disclosed that OIP5-AS1 ameliorated BUP-caused neurotoxicity via regulating the miR-34b/NFAT5 axis, suggesting that OIP5-AS1 might be a promising therapeutic target for the treatment of BUP-induced neurotoxicity.

[Clinical research of electroacupuncture on the analgesic effect of thoracic perioperative stage].

OBJECTIVE: To discuss the clinical therapeutic effects of electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) on the analgesic effect of thoracic perioperative stage and its effect mechanism. METHODS: Sixty cases of esophageal cancer with elective radical resection under general anesthesia were divided into an observation group and a control group according to the operation sequence, 30 cases in each one. In the control group, the general anesthesia was simply applied and sufentanil was administered for patient controlled intravenous analgesia (PCIA) after operation. In the observation group, on the basis of the scheme as the control group, the electroacupuncture was used at Neimadian (Extra) and Neiguan (PC 6) 30 min before anesthesia induction and after operation, with continuous wave, tolerable intensity, lasting for 30 min. Separately, before acupuncture (T1) and 2h (T2), 12h (T3), 24h (T4) and 48h (T5) after operation, the plasma ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were determined. During operation, under the same state (from 50 to 60) of bispectrum of EEG (BIS), the intraoperative anesthetic dose was recorded. Using visual analogue scale (VAS), the pain degree was evaluated at T2, T3, T4 and T5 separately and the grade assessment of the therapeutic effects and safety were recorded at each time point. RESULTS: ①The total dosage of sufentanil in the observation group was less than that in the control group[(1.83±0.56) mg vs (2.54±0.62) mg, P<0.05]. ②VAS scores at T2, T3 and T4 in the patients of the observation group were all lower than those in the control group (all P<0.05). ③The levels of plasma ß-EP at T3, T4 and T5 in the observation group were increased significantly as compared with those in the control group (all P<0.05) and the levels of plasma 5-HT and PGE2 at T2, T3 and T4 were reduced significantly as compared with those in the control group (all P<0.05). ④ The excellent analgesia rates 2h、12h and 24h after operation in the observation group were better than those in the control group (all P<0.05). ⑤The rate of the A grade safety in the observation group was higher than that in the control group (P<0.05). CONCLUSIONS: Electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) provides the safe and effective postoperative anesthesia of thoracic surgery and reduces the dosage of analgesics during the operation, which is possibly related to the increase of endogenous ß-EP and the inhibition on the release of 5-HT and PGE2.