| Streptococcus suis serotype 2(SS2)is a clinically significant zoonotic Gram-positive opportunistic bacterium that causes clinical signs such as meningitis and sepsis in humans and pigs,which poses a serious risk to worldwide healthcare security.There has been research on the involvement of the insulin-like growth factor 1 receptor(IGF-1R),which is important for healthy growth and metabolism,and has been linked to cancer and viral infections,but not yet to the bacteria that cause meningitis.In this study,we showed that Streptococcus suis infection causes IGF-1R expression,which is linked to the pathogenesis of meningitis caused by this bacterium.We also showed that onychotoxin,an IGF-1R inhibitor,can reduce the damage that Streptococcus suis infection causes to the blood-brain barrier(BBB).Therefore,this study will treat Streptococcus suis meningitis based on blocking the IGF-1R signaling pathway.However,small-molecule IGF-1R inhibitors in clinical trials have been limited due to the drawbacks of high toxic side effects,easy development of drug resistance and high price.In addition,there is a need to develop new drugs that can replace or reduce antibiotic resistance due to the large number of drug resistance caused by antibiotic abuse.However,Chinese medicine is moderately priced and has the advantages of being multi-component,multi-path,and less prone to drug resistance and side effects,and has good therapeutic relevance.Therefore,in this study,we will develop a new traditional Chinese medicine preparation(TCM)that inhibit IGF-1R and its related signaling pathways and treat neuroinflammation.We chose sulfadiazine sodium as the control,and investigated the effect of herbal formulas on IGF-1R and the therapeutic effect on mice with meningitis by establishing a model of meningitis caused by SS2 strain SC 19,and investigated the effect of the herbal formula on the permeability of the bloodbrain barrier,mainly as follows:1.This traditional Chinese medicine preparation down-regulated the transcription level of IGF-1R in SC19-infected human brain microvascular endothelial cells and reduce the cell permeability.In this study,the optimal concentration of each drug acting on human brain microvascular endothelial cell(hBMEC)was obtained by detecting the cell viability;the IGF-1R transcript level in SC19-infected hBMEC was significantly restored by the traditional Chinese medicine preparation.An evaluation of the transendothelial resistance value in SC19-infected hBMEC revealed that this traditional Chinese medicine preparation greatly improved the transendothelial resistance value.It provided an important basis for the design of herbal formulas.2.This traditional Chinese medicine preparation treatment attenuated clinical symptoms in SC 19 meningitis mice.In this study,we found that the treatment of SC 19 meningitis mice with the traditional Chinese medicine preparation could improve the survival rate of mice,slow down the weight loss of mice,and significantly reduce the typical symptoms of SC 19 meningitis in mice,such as paralysis,convulsions,convulsions,head tossing,disorganized coat and decreased appetite,etc.In addition,the Chinese herbal formula could reduce the resistance of SC 19 to sodium sulfadiazine and inhibit the proliferation of SC 19 in the brain tissue of mice.The traditional Chinese medicine preparation could also lessen the resistance of SC 19 to sodium sulfadiazine and inhibit the proliferation of SC19 in mouse brain tissue.3.This traditional Chinese medicine preparation inhibited the inflammatory response of SC 19 meningitis mice.In this study,the pathological changes in brain tissue in mice were observed using H&E staining,and the levels of inflammatory factors IL-6,IL-1β,and TNF-α were detected.The results showed that brain tissue lesions in mice treated with the traditional Chinese medicine preparation were significantly improved,and inflammatory factors expression levels were significantly reduced when compared to the attacking group.4.This traditional Chinese medicine preparation down-regulated the transcript level of IGF-1R in the brain tissue of SC19 meningitis mice and improved the blood-brain barrier permeability of mice.In this study,we used Real-time quantitative PCR(qPCR)to detect IGF-1R transcript levels in mouse brain tissues and assessed blood-brain barrier permeability by detecting the extravasation content of Evans Blue in mouse brain tissues of each group.The results showed that the expression of IGF-1R in the brain tissue of mice treated with the drug was reduced to different degrees compared with that in the tapping group,with the most significant in the group treated with the Chinese herbal formula.At the same time,treatment by the Chinese herbal formula significantly reduced the extravasation content of Evans blue in the brain tissues of mice,suggesting that the tender reduced the blood-brain barrier damage caused by Streptococcus suis infection.In conclusion,this study investigated the therapeutic effects of the self-designed traditional Chinese medicine preparation based on blocking IGF-1R on meningitis in SC19infected mice,and found that the traditional Chinese medicine preparation could reduce the clinical symptoms of SC 19-infected mice,enhance the in vivo antibacterial effect of sodium sulfadiazine on Streptococcus suis,reduce the inflammation level in brain tissue,and significantly revert.In addition,the Chinese herbal formula could down-regulate the transcriptional level of IGF-1R in SC19-infected hBMEC and reduce the permeability of cells.In this study,the effects of the traditional Chinese medicine preparation on IGF-1R transcript levels and therapeutic effects in mice with porcine streptococcal meningitis were investigated in vitro and in vivo,providing a new option for the clinical treatment of Streptococcus suis meningitis. |
PDF Full Text Request