Study On The Mechanism Of Shizao Decoction Combined With Cisplatin In The Intervention Of Malignant Ascitic Fluid And Malignant Pleural Effusion

Objective:To observe the effects of Shizao Decoction combined with Cisplatin on the animal model of malignant ascites and malignant pleural effusion and the survival of the model animal,and to explore the underlying mechanism of such effects.Methods:1.Forty Kunming mice were used to replicate the Ehrlich ascites model.The model mice were randomly divided into model group,cisplatin group,Chinese medicine group,Chinese medicine+cisplatin group after established the model successfully.The other 10 mice were taken as a blank group.Chinese medicine group was given Zhengzaotang decoction,cisplatin group was intraperitoneally injected with cisplatin,Chinese medicine+cisplatin group was administered with Shizaotang and intraperitoneal injection of cisplatin,blank group and model group were intragastrically administered with equal volume of normal saline.The animals were sacrificed on the 11^thday.The body weight of the mice was recorded,the amount of ascites and the weight of the spleen and thymus were measured,and the levels of interleukin-2（IL-2）,interferon gamma（IFN-γ）,tumor necrosis factor alpha（TNF-α）,and vascular endothelial growth factor（VEGF）were detected.2.40 Kunming mice were used for survival experiment,and the Ehrlich ascites tumor model was duplicated and the model mice were randomly divided into model group,cisplatin group,Chinese medicine group,and Chinese medicine+cisplatin group.The administration is the same as above,and the administration is continued until the animal dies.The mouse death date was observed and recorded,and the median survival and life extension rate were calculated.3.Forty Wistar rats were randomly divided into model group,cisplatin group,Chinese medicine group and Chinese medicine+cisplatin group.The other 10 rats were used as a blank group.Chinese medicine group was given Zhengzaotang decoction,cisplatin group was intraperitoneally injected with cisplatin,Chinese medicine+cisplatin group was administered with Shizaotang and intraperitoneal injection of cisplatin,blank group and model group were intragastrically administered with equal volume of normal saline.The animals were sacrificed on the 9^thh day.The amount of ascites and the weight of spleen and thymus were measured.The levels of interleukin-2（IL-2）,interferon gamma（IFN-γ）,tumor necrosis factor alpha（TNF-α）and vascular endothelial growth factor（VEGF）were measured.The density of the pleural tissue was observed by CD31 and CD34.Results:1.Compared with the model group,the amount of ascites decreased in the treatment group,and the difference was statistically significant（P<0.01）.Among the groups,the Chinese medicine+cisplatin group had the best effect.Compared with the model group,the spleen index of the cisplatin group decreased,and the difference was statistically significant（P<0.01）.Compared with the model group,the thymus index of the Chinese medicine group increased,the difference was statistically significant（P<0.01）,and the Chinese medicine+cisplatin group also increased,the difference was statistically significant（P<0.05）.Compared with the model group,the levels of IL-2 and IFN-γin the treatment groups were significantly increased,the difference was statistically significant（P<0.01）,and the levels of TNF-αand VEGF were significantly decreased,the difference was statistically significant（P<0.01）.2.Survival experiment results showed that compared with the model group,the life extension rate of each treatment group was significantly increased（P<0.01）,and the life extension rate was the highest in the Chinese medicine+cisplatin group.3.Compared with the model group,the amount of pleural effusion decreased in each treatment group,and the difference was statistically significant（P<0.01）.Among the groups,the Chinese medicine+cisplatin group had the best effect.Compared with the model group,the levels of IL-2 and IFN-γin the treatment groups were increased,and the difference was statistically significant（P<0.01）,and the contents of TNF-α、VEGF were significantly decreased（P<0.01）.Compared with the model group,the levels of NF-κB in the cisplatin group was decreased,and the difference was statistically significant（P<0.05）,the Chinese medicine group and the Chinese medicine+cisplatin group also decreased,and the difference was statistically significant（P<0.01）.Compared with the model group,the spleen index of the Chinese medicine group increased,the difference was statistically significant（P<0.01）.Compared with the model group,the thymus index of the Chinese medicine group increased,the difference was statistically significant（P<0.01）,the Chinese medicine+cisplatin group also increased,and the difference was statistically significant（P<0.05）.The microvessel density of pleural tissue was detected by CD31 markers.Compared with the blank group,the microvessel density of the model group increased,the difference was statistically significant（P<0.01）.Compared with the model group,the microvessel density decreased in each treatment group,the difference was statistically significant（P<0.01）.The microvessel density of pleural tissue was detected by CD34markers.Compared with the blank group,the microvessel density of the model group increased,the difference was statistically significant（P<0.01）.Compared with the model group,the microvessel density decreased in the cisplatin group and the Chinese medicine+cisplatin group treatment group,the difference was statistically significant（P<0.01）,the microvessel density decreased in the Chinese medicine group,the difference was statistically significant（P<0.05）.Conclusion:The combination of Shizao Decoction and Cisplatin can significantly inhibit malignant ascites.The mechanism may be related to the increase of IL-2 and IFN-γcontents,and the decrease of TNF-αand VEGF levels;The combination of Shizao Decoction and Cisplatin can significantly prolong the survival of mice with malignant ascites;The combination of Shizao Decoction and Cisplatin can significantly inhibit malignant pleural effusion.The mechanism may be related to the increase of the levels of IL-2 and IFN-γ,the decrease of the contents of TNF-α,NF-κB and VEGF,the decrease of the microvessel densities of pleural tissue and the permeability area of the serum.