Protective Effect Of Polygonatum Sibiricum On Testicular Injury In Cd-induced Mice

In recent years,cadmium pollution in China has been relatively serious,and both human and animal health have been threatened.The direct harm of cadmium to human and animal organisms is that it can cause serious pathological damages to the liver,kidney,heart,lungs,brain and other organs,especially for testicular.Due to the long half-life of cadmium,it is difficult to discharge once it enters the body.At present,there is no effective drugs for treating cadmium poisoning.Polygonatum Sibiricum is a traditional Chinese herbal medicine and has has the effects of replenishing qi and nourishing yin,strengthening spleen,moistening the lungs,and benefiting the kidneys.And there has not been studied in terms of its effects on testicular structure and function.Therefore,in order to explore the therapeutic effect and mechanism of Rhizoma Polygonati on cadmium-induced testicular damage.In this study,a mouse model of cadmium poisoning was established and Polygonatum Sibiricum was used for treatment.The testicular histological changes,changes in antioxidative parameters,sperm survival rate,sperm deformity rate and molecular level were used to investigate the therapeutic effect and mechanism of Polygonatum Sibiricum on testicular damage in mice infected with cadmium.In this study,120 Kunming mice were used as experimental animals.After adaptive feeding for 7 days,they were randomly divided into 4 groups（including blank group,Huang Jing group,model group and Huang Jing treatment group.）,30 in each group.At the beginning of the experiment,mice in the model group and Polygonatum Sibiricum treatment group were given an intraperitoneal injection of sterile CdCl₂ solution at a dose of 2.5 mg/kg body weight,and the blank group and Polygonatum Sibiricum group were injected with the same amount of physiological saline.The mice of Polygonatum Sibiricum and Polygonatum Sibiricum treated groups were fed 10 g/kg·d body weight of Polygonatum Sibiricum water extract,while the blank group and model group were given equal amount of distilled water.Detection of sperm survival rate,sperm deformity rate,testicular tissue antioxidant-related indicators,cell cycle,ROS levels,serum testosterone levels,histopathological changes,testicular TXNIP,NLRP3,Casepase-1,Cyt-c,Caspase-3,Caspase-9 protein expression and TXNIP,NLRP3,Casepase-1,IL-1β,Cyt-c,Caspase-3,Caspase-9 gene expression.The results:（1）Effect of Polygonatum Sibiricum on testicular function of cadmium-deficient mice:In the model group,testis coefficient,sperm survival rate,serum testosterone level,CAT,T-SOD and GSH activity were decreased,testicular cell apoptosis,testicular cell ROS level,sperm Malformation rate and MDA content were increased,and the cell cycle was arrested in G₀/G₁ phase,which was significantly different from the blank group（P<0.05）.After 35 days of treatment,the testis coefficient,sperm viability,and serum of the Polygonatum Sibiricum-treated mice Testosterone levels,CAT,T-SOD and GSH activities were increased,apoptosis of testis cells,ROS levels in testicular cells,sperm malformation rate,and MDA content were decreased,and cell cycle arrest was restored.There was a significant difference compared with the model group（P<0.05）.There was no significant difference between blank group and Polygonatum Sibiricum group（P>0.05）.（2）Effect of Polygonatum Sibiricum on histopathology of cadmium-deficient mice:In the model group,the number of seminiferous tubules in the testis decreased,the arrangement was disordered,the cell level in the seminiferous tubules decreased,and the levels of spermatogenic cells at all levels were disordered to some extent.After 35 days of treatment with Polygonatum Sibiricum,the damage of testicular tissue was significantly reduced.Compared with the blank group,the number of spermatogenic cells was more and the arrangement was basically neat.With the prolongation of treatment time,the testis structure became normal.（3）Testis inflammasome and apoptosis-related gene expression:TXNIP,NLRP3,Caspase-1,IL-1β,Cyt-c,Caspase-9,Caspase-3 mRNA expression in the testis of the model group was significantly higher than that of the blank group.After being treated with Polygonatum Sibiricum for 35 days,the expression of TXNIP,NLRP3,Caspase-1,IL-1β,Cyt-c,Caspase-9,Caspase-3 mRNA in the testis of the treatment group was significantly higher than that of the model group（P<0.05）.Decreased（P<0.05）,there was no significant difference in mRNA expression between Polygonatum Sibiricum and blank groups（P>0.05）.（4）Testis inflammasome and apoptosis-related protein expression:The expression of NLRP3,Caspase-1,Cyt-c,Caspase-9,Caspase-3 protein in mouse testis of the model group was significantly higher than that of the control group（P<0.05）After 35 days treatment with Polygonatum Sibiricum,compared with the model group,the expression of NLRP3,Caspase-1,Cyt-c,Caspase-9,Caspase-3 protein in the testis tissue of Polygonatum Sibiricum treatment group was significantly reduced（P<0.05）,Huang Jing There was no significant difference in mRNA expression between group and blank group（P>0.05）.Conclusion:Polygonatum Sibiricum has obvious therapeutic effect on CdCl₂-induced testicular injury in mice,which can effectively improve the structure and physiological function of testis.Its mechanism of action is related to regulation of TXNIP-NLRP3-Casepase-1 and Cyt-c-Caspase-9-Caspase-3 signaling pathways.