Objective:To explore the efficacy and mechanism of berberine(BBR)on early brain injury(EBI)in subarachnoid hemorrhage(SAH)rats.Methods:Sixty-eight SD rats were used to establish SAH model through internal carotid artery puncture and randomly divided into three groups:Sham group,SAH model group,and SAH+BBR group.Rats in the SAH+BBR group were given BBR intragastrically at 3 and 6 h after operation,and were treated with BBR twice on the second day.The severity of SAH grade,neurological score,brain edema and blood-brain barrier func-tion were evaluated 48 h after operation.Neuron apoptosis was detected by immunofluorescence staining.The levels of inflammatory factors in brain tissue were assessed by ELISA.NLRP3 inflammasome,ASC and caspase-1 protein expres-sion were investigated by Western Blot.Results:BBR can promote the recovery of neurological impairment(P＜0.05),improve brain edema and blood-brain barrier function(P＜0.05),reduce neuronal cell apoptosis(P＜0.05),and alleviate brain injury in SAH rats.Compared with SAH group,BBR treatment inhibited the expression of NLRP3 inflammasome,ASC,and caspase-1(P＜0.05).Moreover,BBR decreased the levels of IL-1β,IL-6,and TNF-α in brain tissue(P＜0.05).Conclusion:BBR may reduce the inflammatory response of brain tissue by regulating the acti-vation of NLRP3 inflammasome,thus alleviating the early brain injury after SAH.

Objective:To explore the efficacy and mechanism of berberine(BBR)on early brain injury(EBI)in subarachnoid hemorrhage(SAH)rats.Methods:Sixty-eight SD rats were used to establish SAH model through internal carotid artery puncture and randomly divided into three groups:Sham group,SAH model group,and SAH+BBR group.Rats in the SAH+BBR group were given BBR intragastrically at 3 and 6 h after operation,and were treated with BBR twice on the second day.The severity of SAH grade,neurological score,brain edema and blood-brain barrier func-tion were evaluated 48 h after operation.Neuron apoptosis was detected by immunofluorescence staining.The levels of inflammatory factors in brain tissue were assessed by ELISA.NLRP3 inflammasome,ASC and caspase-1 protein expres-sion were investigated by Western Blot.Results:BBR can promote the recovery of neurological impairment(P＜0.05),improve brain edema and blood-brain barrier function(P＜0.05),reduce neuronal cell apoptosis(P＜0.05),and alleviate brain injury in SAH rats.Compared with SAH group,BBR treatment inhibited the expression of NLRP3 inflammasome,ASC,and caspase-1(P＜0.05).Moreover,BBR decreased the levels of IL-1β,IL-6,and TNF-α in brain tissue(P＜0.05).Conclusion:BBR may reduce the inflammatory response of brain tissue by regulating the acti-vation of NLRP3 inflammasome,thus alleviating the early brain injury after SAH.

ObjectiveTo investigate the analgesic effect and mechanism of Osteoking （OK） on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion （CCD） was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group， low， medium， and high dose OK groups （1.31， 2.63， 5.25 mL·kg^-1·d^-1）， and pregabalin group （5 mg·kg^-1）， with eight rats in each group. Another eight SD rats were taken as the blank group， and the same volume of normal saline was given by gavage. Behavioral tests， side effect evaluation， network analysis， Western blot， immunofluorescence， and antagonist application were used to explore the effect. ResultCompared with the blank group， the mechanical hyperalgesia threshold， thermal hyperalgesia threshold， and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased （P<0.01）， and the related indicators of the affected foot footprints are significantly down-regulated （P<0.01）. The expression of signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， and phosphorylated extracellular regulated protein kinase （p-ERK） in microglia in the spinal dorsal horn is significantly increased in the model group （P<0.01）. Compared with the model group， low， medium， and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats （P<0.05， P<0.01） in a dose-dependent manner， improve the gait of CCD rats （P<0.05， P<0.01）， and reduce the expression of inflammatory factors in the spinal dorsal horn （P<0.05， P<0.01）. The expression of STAT3， VEGFA， and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased （P<0.05， P<0.01）， and the acetic acid-induced nociceptive response in rats is effectively reduced （P<0.05， P<0.01）. In addition， there is no tolerance. The results of the body mass test， organ index， forced swimming， and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group （P<0.01）. ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects， and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3， VEGFA， p-ERK， and other elements in microglia.

Objective To investigate the therapeutic effect of 4-1BB monoclone antibodies on mice hepatitis induced by Coneanavalin A (ConA) and its influenes on CD4+CD25+T lymphoeytes during the course. Methods The miee model of hepatic injury was indueed by ConA and monitored by hepatic function tests and hepatic pathology. The expressions of 4-1BB were examined by flow eytometry. 4-1BB monoelone antibodies were intravenously injected to the mice. The therapeutic efficacy was then examined by hepatic function tests and hepatic pathology. The expressions of CD4+CD25+T lymphoeytes were also examined by flow eytometry. Results The group of immune hepatic injury induced by ConA showed damage and marked increase of ALT and AST which were (139±22) U/L and (130±16) U/L respectively. The expression level of 4-1BB was 8.1±2.6. Compared with the eontrol group, the difference was significant (P<0.05). The overall eondition of the miee was improved after being treated with 4-1BB monoelone antibodies. ALT and AST were lowed down to (98±14) U/L and (89±11) U/L respectively and the differenee was signifieant (P<0.01). The expression of 4-1BB of the control group was 3.0±0.8 and that of the treatment group was 8.3±3.0. The difference was significant (P<0.01). Conclusion 4-1BB eontributes to the immune-mediated hepatic injury induced by Con-A.