| Objective:The experiment objective is to study the different effects on cancer cachexia among indomethacin, thalidomide, fish oil, fish oil plus thalidomide and nutritional support by establishing an cancer cachexia model. This experiment observe the changes of nutritional indexes (total protein,blood sugar , triglyeride,cholesterin),cytokines (TNF-α, IL-6) and activity of nuclear factor-kappa B to compare the curative effect and mechamisms of those drugs.Methods:The animal model of experiment about cancer cachexia was established by inoculating BALB/C mice on right armpit subcutaneously with colon 26. 80 male BALB/C mice were divided into 8 groups randomly: health control (HC) group, cancer cachexia (CC)group, medroxyprogesterone (MPA) group,indomethacin (IND)group , thalidomide(TLD)group, fish oil (EPA) group, indomethacin plus fish oil (IND+EPA), nutritional support (NS) group. Mice of each group were treated for one week. Observations were made on the changes of body weight, eating and drinking and tumor volum. Meanwhile the biochemical indicator were measured by automatic biochemistry analyzer, the serum level TNF-αand IL-6 were measured by radio immunoassay, the activity of NF-κB in spleen . The data were analyzed with SPSS 12.0 software, including T-test , Q-test, ANOVA. And the data were showed in the form of x±s.Results:1 Animal model3-5 days later, the tumor could be touched on the tumor bearing mice. Meanwhile ,the sprit of the mice became bad, the action of the mice decreased. But the changes of food and drink of the mice were not obviously. 14 days later, the tumor bearing mice became thin,skin and fur became coarse,dark and gloomy. Their activities were slower than before and the sprit became worse. Drinking and eating reduced obviously. All the mice were in condition of cancer cachexia. After intervened by drugs for 3 or 4 days, the sprit of the tumor bearing mice became better, the action became active, the hair also take on a new look, the eating and drinking increased relatively. But the tumor didn't grow downwards.2 Non-tumor weight and tumor weightThe non-tumor weight of all the tumor bearing mice decreased gradually after inovulated tumor cell. On the fifteenth day, the mean non-tumor weight in the tumor bearing mice became lower than that in healthy mice(P<0.05), all the mice were in condition of cancer cachexia. The mice were executed on the twenty-third day.The non-tumor weight in the tumor bearing mice much lower than that in healthy mice(P<0.001). The non-tumor weight in the"IND","EPA"group heavier than that in"NS"group (P<0.05).There was no significant difference in the tumor weight among all the tumor bearing groups(P>0.05).3 Biochemical indicatorThe serum level of total protein in"CC"group was not lower than that in"HC"group (P>0.05). But the blood sugar in"CC"group was much lower than that in"HC"group (P<0.05). The triglyeride and cholesterol in"CC"group were much higher than that in"HC"group (P<0.05).The blood sugar in"IND"group was highest than that in all other groups that were interfered(P<0.05) , and there was no significant difference between"IND"group and"MPA"group(P>0.05). There was no significant difference in blood sugar between"NS"group and"CC"group(P>0.05). The blood sugar in"EPA","TLD","IND +EPA"group was higher than that in"CC"group, but there was no significant difference(P>0.05).The serum level of triglyeride in"TLD","EPA", and"EPA+IND"was much lower than that in"CC"group(P<0.05). But there was no significant difference in the serum level of triglyeride between"IND","NS"group and"CC"group(P>0.05). And there was no significant difference in the serum level of triglyeride between"TLD","EPA"group and MPA"group(P>0.05). The serum level of triglyeride in"EPA+IND"group was much lower than that in"MPA"group(P<0.05).The serum leve of cholesterol in groups that were treated was much lower than that in"CC"group(P<0.05). The serum level of cholesterol in"EPA"and"EPA+IND"group was lower than that in"MPA"group(P<0.05). The serum level of cholesterol in"TLD"group was higher than that in"MPA"group(P<0.05). There was no significant difference in serum level of cholesterol between"IND","NS"group and"MPA"group(P>0.05).4 CytokinesThe serum level of TNF-αand IL-6 in"CC"group was higher than that in"HC"group(P<0.05). The serum level of TNF-αin"IND","EPA","EPA+IND","TLD"and"NS"group was much lower than that in"CC"group(P<0.05). There was no significant difference in serum level of TNF-αbetween"IND","EPA","EPA+IND","TLD","NS"groups and"MPA"group(P>0.05). The serum level of TNF-αin"IND"and"NS"group was higher than that in"EPA","EPA+IND", and"TLD"group(P<0.05). The serum level of IL-6 in the group that be treated was much lower than that in"CC"group(P<0.05). And that in"NS"group was higher than that in"MPA"group(P<0.05). And there was no significant difference in serum level of IL-6 between"IND","EPA","EPA+IND","TLD"group and"MPA"group(P>0.05).5 The activity of NF-κB in spleenThe activity of NF-κB in spleen in"CC"group was more strengthened than that in"HC"group(P<0.05). The activity of NF-κB in spleen in"IND","EPA","IND+EPA","TLD"group was much weaker than that in"CC"group(P<0.05), but there was no significant difference among themselves(P<0.05). There was no significant difference in activity of NF-κB in spleen between"NS"group and"CC"group(P>0.05). The relationship between the activity of NF-κB in spleen and density of cytokines was linear correlation.6 Pathological section of tumorLM: Tumor cell filled the section, disordered arrangement, the size of tumor cell varied from each other, the appearance of the tumor cell was irregular, it was clear that tumor giant cell, the nuclear of the tumor cell was big , anachromasis, mitotic figure increased, karyoplasmic ratio increased.Conclusions:1 The body weight of mice decreased obviously after going into the condition of cancer cachexia ( >5%), accompanying the symptom of bad spirit , less activity, less eating and drinking, and so on.2 Malnutrition and metabolic disorder occurred in the cancer cachexia mice. the serum level of cytokines (IL-6,TNF-α) and the activity NF-κB in spleen increased.3 The drugs could not obviously increased the non-tumor weight of mice.4 The drugs could not improve the condition of lower protein .5 The effect of increasing the blood sugar by"IND"was best, but not superior to"MPA". The effect of decreasing the triglyeride by"IND+EPA"was best, and superior to"MPA". The effect of decreasing the cholesterol by"IND+EPA"and"EPA"was best, and superior to"MPA".6 All the durgs could decreased the serum level of TNF-αand IL-6.The effect of decreasing the serum level of TNF-αof all the drugs was weaker than MPA.The effect of decreasing the serum level of IL-6 by"NS"was weaker than MPA, and there was no significant difference between"IND""EPA""IND+EPA""TLD"and"MPA".7 The activity NF-κB in spleen increased obviously in the condition of cancer cachexia. All the drugs could inhibited the activity NF-κB in spleen except NS. |
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