Effect Of Xiaotan Sanjie Decoction In Protein Metabolic In Tumor-bearing Rats

Background:Metabolic abnormalities which are the important complications of malignant tumor are one of the reasons for difficult treatment and bad prognosis. Adjusting metabolic abnormalities is the key to elevate patients'survival quality. Phlegm pollution hypothesis proposed by Professor Wei-Pinkang is said that the reason for metabolic abnormalities is muddy phlegm. It is already confirmed that tumor protein metabolic abnormalities are relevant to inflammation. Prof. Wei has established his theory of "dispersing phlegm and dissipating bind" in clinically treating patients with tumors. Therapeutic effect is satisfactory. So the purpose of this study is to discover the mechanism of Xiaotan Sanjie Decoction adjusting tumor protein metabolic abnormalities in a more comprehensive and convincing way by regulating the expressions of different inflammatory factors in the tumor-bearing rats.Objective:The study was designed to investigate the mechanism of Xiaotan Sanjie Decoction in tumor protein metabolic abnormalities and prove scientific nature of the theory of tumor phlegm syndrome and material existence of environment polluted by phlegm "muddy phlegm" promoting the tumor metabolic abnormalities. To construct environment polluted by phlegm by establishing subcutaneous model of Carcinosarcome Walker 256 in Wistar rats and by the methods of ELISA, Envision, realtime-PCR to detect the expressions of inflammatory factors'(TNF-a, IL-6, ect) mRNA and encoded protein regulated by Xiaotan Sanjie Decoction.Methods:30 Wistar mice were randomly divided into normal group, no-drugs group and Xiaotan Sanjie Decoction group. The rats were made subcutaneous model of Carcinosarcome Walker 256 except the rats in normal group to establish tumor protein metabolic abnormalities model. The rats in Xiaotan Sanjie Decoction group were applied with herbs 24 hours after the surgery (2ml/d,×4w); normal group and no-drugs group were raised in the same condition and with common food and drink. The weight was observed. The experiment was terminated on the 4th week.The rats were sacrificed after blood sampling collected from heart. The total protein and albumin were detected. The expressions of mRNA and encoded protein of TNF-a, IL-6, NF-Kb and Ubiquitin were detected by the methods of ELISA, Envision and Realtime-PCR.Results:1. We built subcutaneous model of Carcinosarcome Walker 256, the lump could be touched in the Subcutaneous 7 days after modeling and increas gradually. Rats bearing tumor emerged exhausted symptoms of dried-up coat, less food, athrepsy, lassitude and slowly action. The HE staining illustrated the structural disorder of skeletal muscle.2. Rats bearing tumor grew slowly because of tumor. Their weight were lower than normal group 7 days after modeling(P<0.05); Xiaotan Sanjie Decoction group's was higher than that of no-drugs group (P<0.05) but was lower than normal group 21 days after modeling (P<0.05)3. Total protein and albumin exam showed:compared with normal group, total protein of no-drugs group and Xiaotan Sanjie Decoction group were not lower (P>0.05). Albumin of all rats bearing tumor was decreased (P<0.05). Albumin of Xiaotan Sanjie Decoction group's was higher than that of no-drugs group (P<0.05).4. The results of Xiaotan Sanjie Decoction affecting the expressions of serum TNF-a protein showed:the expressions of serum TNF-a protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of serum IL-6 protein showed:the expressions of serum IL-6 protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)5. The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a protein in muscle tissues showed:the expressions of TNF-a protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a mRNA in muscle tissues showed:the expressions of TNF-amRNA in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a protein in livers showed:the expressions of TNF-a protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)6. The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 protein in muscle tissues showed:the expressions of IL-6 protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05).The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 mRNA in muscle tissues showed:the expressions of IL-6 mRNA in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 protein in livers showed:the expressions of IL-6 protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)7. The results of Xiaotan Sanjie Decoction affecting the expressions of NF-Kb protein in muscle tissues showed:the expressions of NF-Kb protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of NF-Kb mRNA in muscle tissues showed:the expressions of NF-κb mRNA in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)8. The results of Xiaotan Sanjie Decoction affecting the expressions of Ubiquitin protein in muscle tissues showed:the expressions of Ubiquitin protein in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)The results of Xiaotan Sanjie Decoction affecting the expressions of Ubiquitin mRNA in muscle tissues showed:the expressions of Ubiquitin mRNA in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)Conclusion1. The subcutaneous model of Carcinosarcome Walker 256 in rats, which is made simply and has a high successful rate, is similar to the biological features of tumor protein metabolic abnormalities.2. Xiaotan Sanjie Decoction can conspicuously inhibit the weight lost of tumor-bearing rats.and Improve the level of serum albumin of tumor-bearing rats.3. They are confirmed that inflammation is correlated to tumor protein metabolic abnormalities, phlegm pollution hypothesis about tumor metabolic abnormalities is scientific and muddy phlegm exists corporeally, because the expressions of inflammatory factors increasing in serum, liver and muscle tissues.4. Xiaotan Sanjie Decoction can down-regulate the expressions of TNF-a and IL-6 in liver of tumor-bearing rats, regulation of liver protein synthesis. Down-regulate the expressions of ubiquitin in muscle tissues of tumor-bearing rats, and regulat skeletal muscle ATP-ubiquitin-proteasome. This may be one of the mechanisms of Xiaotan Sanjie Decoction adjusting tumor metabolic abnormalities and clearing phlegm polluted environment.