| Objective: Cisplatin is commonly used as a chemotherapy drug,it has a good clinical effect in the treatment of various solid tumors such as prostate cancer,lung cancer,breast cancer,and esophageal cancer.However,in the course of chemotherapy,nausea,vomiting,tinnitus,tachycardia,nephrotoxicity,hepatotoxicity and other adverse reactions often occur.It can affect the therapeutic effect of tumor patients or leave sequelae.From the point of view of the Chinese medicine,the toxicity of cisplatin is easy to make patients exhausted and weakened,and it damages Shen and Pi in Chinese medicine.Da Bu Pi decoction from Dunhuang ancient prescriptions has the functions of invigorating vital energy and Jianpi Zishen.Based on the theory of Chinese Medicine,it should be treated according to the corresponding symptoms of cisplatin toxicity,so we choose Da Bu Pi decoction to relieve the toxicity of cisplatin.Methods: Sixty Kunming mice were randomly divided into(1)normal saline group: give equal volume of normal saline;(2)model group: mice were injected with cisplatin injection(2mg/kg body weight/ time),once every three days,a total of six times;(3)cisplatin+high-dose herbs group;(4)cisplatin+medium-dose herbs group;(5)cisplatin+low-dose herbs group;three groups above were treated with Da Bu Pi decoction during the cisplatin injection,0.7mL,0.5mL and 0.25 mL were given to mice,twice a day(morning and evening).(6)Chinese medicine control group: 0.5mL decoction/time,twice a day.Later,mice were closely observed.After thirty days of treatment,we investigated the weights,kidney coefficients and liver coefficients of mice.Biochemical indexes of serum creatinine(Scr),urea nitrogen(BUN),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TRIL)were detected.And the pathological changes of kidneys and liver tissues in mice were checked by HE staining section.The mRNA expressions of TNF-? in renal tissues were tested by real-time fluorescent quantitative PCR(RT-PCR).The serum TNF-? of the mice were measured by enzyme-linked immunosorbent assay(ELISA).Results:(1)In model group,the amount of diet and water decreased day by day,mice had lost weight noticeably,thin stool soft and the body surface temperature were lower.Aftertreatment of Chinese Medicine,mice dietary and water increased,and their had significantly improved mental state,body mass,stool status.(2)The body weight,kidney coefficient and liver coefficient of the model group were 30.0±1.41 g,0.0109±0.10% and 0.0325±0.10%respectively.Above data of the cisplatin+high-dose herbs group were 38.3±0.91 g,0.0113±0.11% and 0.0332±0.14% respectively.Compared with model group,the indications of cisplatin+high-dose herbs group were significantly improved(P<0.01).(3)Biochemical indicators of renal function: the contents of Scr in normal saline group,model group,cisplatin+high-dose herbs group,cisplatin+medium-dose herbs group and cisplatin+low-dose herbs group were 134.00±9.31?mol/L,186.00±12.44?mol/L,146.00±8.12?mol/L,159.00±12.32?mol/L and 191.00±8.76?mol/L respectively.Compared with model group,the contents of high-dose herbs group and medium-dose herbs group were decreased significantly(P < 0.01).Above groups BUN were 4.79±7.64mmol/L,5.71±7.47mmol/L,3.43±5.15mmol/L,4.83±6.37mmol/L,5.38±5.89mmol/L respectively.Compared with model group,the data of high-dose group and medium-dose group were down.(4)Biochemical indicators of liver function: ALT in model group(144±10.29U/L)was significantly higher than normal saline group(89±7.48U/L).The high-dose group(91±13.84U/L)was significantly lower than model group(P<0.01),also the medium-dose herbs group(105±9.39U/L)got lower(P<0.05).AST in normal saline group,model group,cisplatin+high-dose herbs group,cisplatin+medium-dose herbs group and cisplatin+low-dose herbs group were 114±10.37U/L,201±14.61U/L,87±13.89U/L,137±13.18U/L,193±15.48U/L respectively.Compared with model group,the contents of high-dose herbs group and medium-dose herbs group were decreased.TRIL in model group is 17.35±6.35?mol/L,the high and medium-dose groups of Chinese medicine(13.59±4.77?mol/L and 13.85±6.82?mol/L)were decreased compared with model group.(5)In model group,capillary hyperplasia in the glomeruli,inflammation and infiltration of the renal interstitium,hepatocytes swelled significantly,vacuoles formed in the cytoplasm,central venous congestion.After treatment of Chinese Medicine,the pathological damages of kidney and liver tissues got alleviated.(6)The expression level of TNF-? mRNA in model group was about 64 times higher than normal saline group(P<0.01).The expression level of TNF-? mRNA in the cisplatin+high-dose herbs group was about 1/3 of the model group,which was significantly reduced(P<0.01).The expression of TNF-? mRNA in middleand low-dose group were no significant difference compared with model group(P>0.05).(7)The serum TNF-? content of mice in normal saline group was 3.57ng/L,while it was15.33ng/L in model group,which was significantly increased(P < 0.01).The value in the cisplatin+high-dose medicine group was 12.65ng/L,it was significantly decreased(P<0.01).There was no significant change in the content of middle and low-dose herbs group(P>0.05).Conclusion:(1)After the treatment of Da Bu Pi decoction from Dunhuang ancient prescriptions,the contents of serum creatinine(Scr)and urea nitrogen(BUN)related to renal function in mice were significantly reduced,the degree of pathological damages in kidney tissues were alleviated,the mRNA expression level of inflammatory factor TNF-? and the content in serum were significantly reduced,and the inflammation of kidney was inhibited.This prescription can protect the kidney from cisplatin toxicity.(2)After the intervention of Da Bu Pi decoction from Dunhuang ancient prescriptions,the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TRIL)related to liver function in mice were significantly reduced.It proved that this prescription could also reduce the liver damage caused by cisplatin.(3)In this study,Da Bu Pi decoction showed its protective functions for kidney and liver from cisplatin toxicity.It is proved that Da Bu Pi decoction may have some clinical value in reducing cisplatin toxicity. |
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