| Objectives Before(prophylactic intervention)and after(therapeutic intervention)the Wistarrat transplanted hepatocellular carcinoma model was established,selenium and beta-carotene was given alone or in combination in two period.To observe the effect of two kinds of intervention substances on the physiological function of rats and the effect on the occurrence and develoment of liver cancer,so as to provide new ideas for the prevention and treatment of liver cancer.Methods1 The preventive stage:Before the Wistar rat transplanted hepatocellular carcinoma odel was established,beta-carotene and selenium was given alone or in combination 4 weeks according to body weight every day.Selenium experimental group(sodium selenite 0.3mg/(kg·d)),beta-carotene experimental group(beta-carotene 10mg/(kg·d)),beta-carotene and selenium combined group(sodium selenite 0.3mg/(kg·d)+ beta-carotene 10mg/(kg·d)),the control group(water0.3mg/(kg·d)+ oil 10mg/(kg·d)).The general physical signs of rats were observed during preventive intervention,the food intake was recorded dailyand the weight of each 48 h was recorded.10 rats were sacrificed in each group after 30 days,blood samples were collected to detect the serum biochemical indexes,serum and liver tissue antioxidant markers(T-SOD,GSH-Px,MDA)and the organ coefficient was calculated.2 The remaining 56 rats(14 × 4groups)was established a transpanted hepatocellular carcinoma model by laparotomize,the behavioral signs of the rats were observed for one week.3 On the eighth day after modeling,the experimental group continued to give the corresponding intervention substances.When the rats death occurs,the rats were killed and blood samples were collected to detect the blood routine,blood biochemistry,serum and liver tissue antioxidant indexes(T-SOD,GSH-Px,MDA)and calculate the organ coefficient.The expression of Bcl-2 and Bax protein in liver tissue was detected by Western Blot.Results1 Preventive stage1.1 Rat general signsIn the prophylactic stage,the rats in each group were normal hair,and there was no abnormal secretions in the eyes and mouth,and the mental activity was normal.1.2 Body weight,food intake and food utilization situationIn the preventive stage,the body weight of rats in each group was gradually increased.The weight gain of second weeks in the Se group was less than that in the combined group and the control group(P<0.01).There was no significant difference in food intake and food utilization rate in each group.1.3 Organ coefficientThe liver organ coefficient of Se group is higher than that in the ?-C group(P<0.05),spleen coefficient of Se group is higher than that in the ?-C group and the combined group(P<0.01);female rats: lung organ coefficient of combined group is higher than that in the control group(P<0.05),ovarian organ coefficient of Se group is higher than that in combined group(P<0.05).1.4 Blood biochemical indexesThe ratio of direct bilirubin and indirect bilirubin: ?-C group is lower than that in the control group(P<0.05),?-C group is lower than that in the Se group and the combined group(P<0.01);the value of globulin in ?-C group and combined group are higher than that in control group(P<0.05);the value of BUN in combined group is lower than that in ?-C group(P<0.05);there is no significant difference in the blood glucose and lipid metabolism of rats in groups.1.5 Serum and liver tissue antioxidant index1.5.1 Serum antioxidant indexThere was no significant difference in serum antioxidant indexes(T-SOD?GSH-Px?MDA)in each group.1.5.2 Antioxidant index of liver tissueT-SOD activity of Se group and combination group are less than that in the control group(P<0.01)and ?-C group is higher than that in the control group(P<0.05),Se group is less than the combined group and ?-C group,?-C group is higher than combined group(P<0.01);GSH-Px activity of Se group and combined group are lower than the control group(P<0.01),?-C group is higher than the control group(P<0.01),Se group and combined group is lower than ?-C group(P<0.01);MDA content result:there was no significant difference in each group.1.6 Pathological changesIn the Preventive stage,the liver tissue of the rats is normal in each group.2 Establishment of transplanted hepatocellular carcinoma modelAll the rats showed different degrees of depression,hair loss,food intake and weight loss after inoculation,two rats were selected to kill and dissect,the tumor nodules were found in the vicinity of the liver of each rat.Transplanted hepatocellular carcinoma model was established successfully.3 Therapeutic intervention stage3.1 General signs of ratsThe basic situation of the rats was consistent with the stage of prevention,but individual rats appear blood secretion in their noses and mouths,abdominal swelling and difficult moving and so on.3.2 Body weight,food intake and food utilizationWeight: male weight:?-C group and combined group is higher than the control group(P<0.01)in the first week;Se group and ?-C group is higher than the control group(P<0.05)in the third week;Se group is higher than the control group and the combined group(P<0.05)in the fourth week.Body weight loss between before and after inoculation,?-C group lost weight is higher than Se group,combined group and the control group;female weight: the weight loss of Se group is higher than that of control group(P<0.05)between before and after inoculation.Food intake: the Se group was more than the control group and the combined group(P<0.05)in female rats before inoculation.Food utilization: there was no significant difference in the food utilization.3.3 Organ coefficientThe organ coefficient of male rats: the spleen organ coefficient of ?-C group is less than that of the combined group(P<0.05).Female organ coefficient: lung organ coefficient of combined group is higher than the Se group,?-C group and control group(P<0.01),Se group is lower than the control group(P<0.05);liver organ coefficient of Se group and ?-C group are lower than the control group(P<0.05),Se group and ?-C group is less than combined group(P<0.05);the spleen organ coefficient of Se group is less than the ?-C group(P<0.05);the right kidney coefficient of Se group and combined group are lower than the control group(P<0.05).3.4 Blood routine and blood biochemistry3.4.1 Blood routine indexPlatelet-large cell ratio of combination group was greater than the control group(P<0.05)and the Se group was less than the combined group(P<0.05);white blood cell related indicators: there was no significant difference between these groups.3.4.2 Blood biochemical indexesThe value of total protein: Se group is lower than the control group(P<0.01),Se group is less than ?-C group and combined group(P<0.05);Globulin value: Se group is less than the control group(P<0.01),Se group is less than the ?-C group and combined group(P<0.05);BUN value:Se group is higher than ?-C group(P<0.05);there is no significant difference between the groups in blood glucose and lipid metabolism.3.5 Serum and liver tissue antioxidant index3.5.1 Serum antioxidant indexThere was no significant difference in serum antioxidant indexes in each group.3.5.2 Antioxidant index of liver tissueT-SOD activity situation: Se group is higher than the control group(P<0.01),combined group is higher than the control group(P<0.05),?-C group is higher than Se group(P<0.01),the control group(P<0.01)and combined group(P<0.05);GSH-Px activity of Se group,?-C group and combined group are higher than the control group(P<0.01)and combined group is higher than Se group and ?-C group(P<0.01);MDA content situation:Se group is higher than the control group,?-C group and combined group(P<0.01),?-C group is higher than the control group(P<0.01)and combined group(P<0.05).3.6 Pathological changesThere are pathological structure damage in rats liver after the inoculation.3.7 Protein expression in liver tissueThe expression of Bcl-2protein in Se group is higher than that in the control group(P<0.05)and combined group(P<0.01)and the combined group is less than the control group(P<0.05)and?-C group(P<0.01).The expression of Baxprotein in ?-C group and combined group are higher than that in Se group(P<0.05).The ratio of Bcl-2and Bax: the combined group is less than the control group,Se group and the ?-C group(P<0.01),?-C group and the combined group are less than the control group(P<0.01),Se group is higher than the control group,combined group and?-C group(P<0.01).Conclusions1 Growth and development of rats are good in the preventive stage in each group,selenium and ?-carotene intake have no adverse effects on normal growth and development of rats,these two substances do not cause harmful irritation or oxidative damage to rats.?-carotene can improve the antioxidant capacity of rat liver.2 In this study,it is feasible to establish the Walker-256 transplanted hepatocellular carcinoma model in Wistar rats by laparotomy.After the establishment of transplanted hepatocellular carcinoma model,the rats were invaded by tumor cells and body appeared a series of disease reaction,the corresponding many body function also appeared disorder change.3 The prevention and treatment of rats with Se and ?-arotene can increase antioxidant capacity of the body,the combination of the two substance can reduce the expression of Bcl-2protein in liver tissue,increase Bax protein expression and promote apoptosis of tumor cells,these two substances are beneficial to the prevention and treatment of liver cancer.4 Selenium has a bidirectional biological regulation effect on physiological function of the body and prevention and treatment liver cancer,its safe dose and the way of application need to be further discussed. |
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