Effect And Mechanism Of Curcumin On Cardiopulmonary Function After Spinal Cord Injury In Rats

Objective:To explore the effect of curcumin(CUR)on the changes of heart and lung function after spinal cord injury in rats and its molecular mechanism,and to elucidate the role of curcumin in improving heart and lung dysfunction induced by spinal cord injury in rats through the ST2 / IL-33 inflammatory signal transduction pathway.These provide a solid theoretical and pharmacodynamic basis for the clinical use of curcumin to treat heart and lung function injuries after spinal cord injury in rats.Methods:A total of thirty SD female rats were randomly selected and weighed after1 week of adaptive feeding with basic feed.The above-mentioned rats were divided into3 groups using random number table method,namely sham operation group(Sham,n=10),model group(SCI,n=10)and curcumin group(CUR,n=10,70 mg / kg),with 10 rats in each group.Both the model group and the curcumin group used Allen's blow method to construct a rat spinal cord injury model.After successful modeling,the rats in curcumin group were drug intervened by 70 mg / kg curcumin gavage,while saline is used for the model group in the same scheme.The rats in sham operation group were fed basic feed and given same amount of saline instead of drug intervention.After 2 weeks of drug intervention,all subjects were evaluated to obtain the effect of curcumin on the motor function of hindlimb of spinal cord injured rats by the BBB score and the Rivlin inclined plate test;the morphology changes of spinal cord,heart and Lung tissue were observed by H&E staining method;the improvement of heart and lung function indices,such as stroke volume(SV),cardiac output(CO),pulmonary artery pressure(PASP),ejection fraction(EF),partial arterial oxygen pressure(PaO ?),partial arterial carbon dioxide pressure(PaCO?)and arterial oxygen saturation(SaO?),were detected.At the same time,enzyme-linked immunosorbent assay(ELISA)was used to detect the heart and lung function indexes sST2 and NT-proBNP,as well as the representation changes of inflammatory indexes IL-6,IL-1?,IL-33 and TNF-?.In addition,real-time quantitative PCR(qRT-PCR)and Western blot were used to detect sST2 / IL-33 inflammatorysignaling molecules in heart and lung tissues and spinal glial fibrillary acidic protein(GFAP),vimentin(Vim)and Chondroitin Sulfate Proteoglycan(CSPG3)protein expression changes,respectively.All data were analyzed and processed using SPSS 24.0statistical software and Graphpad prism 7 software,where P < 0.05 indicates that the difference has significant statistical significance.Results:1.The results of the BBB score showed that the hindlimb motor function scores of the SCI group and the CUR group are significantly lower than those of the Sham group(P <0.01).More detailed,on the 3rd day after operation,the BBB score of the CUR group was higher than that of the SCI group,but with no statistical significance;on the 7th and 14 th day after the operation,the BBB score of the CUR group was obviously higher than that of the SCI group(P < 0.05).The results of the Rivlin slanted plate shows that on 14 th day after surgery,the mean value of the critical level of the slanted plate in the CUR group was higher than that in the SCI group(P < 0.05),which indicates that curcumin can promote the recovery of hindlimb motor function for spinal cord injured rats.2.The results of H&E staining showed that after spinal cord injury,the spinal cord tissue structure was destroyed,and inflammatory cell infiltration and nerve fiber disorder occurs.The curcumin can improve neuronal damage after spinal cord injury in rats,which indicates that curcumin can significantly relieve spinal cord injury and pathological damage of rat spinal cord,heart and lung tissues.3.The results of heart and lung function indicators showed that compared with the sham operation group,the rats in SCI group had a great decline on heart and lung function after spinal cord injury,which is given by the significant decrease of the performance indicators of rats,including SV,PASP,EF,PaO?,PaCO?and SaO?,where the difference was statistically significant(P < 0.05).Compared with the SCI group,the heart and lung function of spinal cord injured rats in the curcumin group were significantly enhanced,which suggests that curcumin can significantly improve the heart and lung function.4.The results of ELISA detection of serum inflammatory factors and sST2 / IL33 inflammatory signal molecule showed that compared with the sham operation group,the SCI group has a statistically significant increase on the expression of inflammatoryfactors IL-6,IL-1?,IL-33 and TNF-?,and the inflammatory signaling molecules sST2 and NT-proBNP3 in serum.Compared with the SCI group,the indicators above were significantly reduced,and the difference was statistically significant(P < 0.05),which suggests that curcumin can inhibit inflammatory reaction in spinal cord injured rats' bodies.5.The results of Western blot for the inflammatory signaling molecules sST2 and IL-33 showed that the SCI group has a notable increase on the protein expression levels comparing with Sham group.Compared with the SCI group,such a level decreased obviously in the curcumin group,and the difference was statistically significant(P <0.05),which indicates that curcumin can significantly inhibit the sST2 / IL33 inflammatory signal in rats with spinal cord injury.6.The results of qRT-PCR and Western blot methods to detect the glial scarformation showed that compared with the sham operation group,the SCI group had up-regulated expressions on GFAP,Vim and CSPG3.Compared with the SCI group,all three levels were significantly reduced.These differences were statistically significant(P< 0.05),which implies that curcumin can inhibit the formation of glial scars in injured rats.Conclusion:1.Curcumin can significantly enhance the recovery of hindlimb motor function of spinal cord injury rats and reduce the pathological damage of spinal cord,heart and lung tissues.2.Curcumin may enhance the heart and lung function of rats with spinal cord injury by inhibiting sST2 / IL33 inflammatory signal expression.3.Curcumin can appreciably inhibit the expression of inflammatory factors and sST2/ IL33 inflammatory signaling molecules in several injured rats.4.Curcumin can obviously discourage the formation of spinal cord glial scars in rats with spinal cord injury.