| Objective: To investigate the effects of inhibition and Immunor-egulatory function on triterpene compound of Cortex Periplocae N-nitrosomethylbenzylamine induced esophageal tumorigenesis in F344 rats. which are helpful for finding the effective therapeutic measures for curing of human esophageal carcinoma. Meanwhile,which provide us with some experimental bases to develop and exploit Chinese medicine herb of triterpenes compound of Cortex Periplocae .Methods:1 Experimental design and dividing group1.1 141 rats were randomly divided into five experimental groups: normal control group, soy oil control group, model group,high dose treated group, low dose treated group.1.2 The administration of drugs was scheduled as blow: The rats in normal control group were freely fed water and food;The rats in soy oil control group were injected soy oil 1ml/kg(i.m.); The rats in model group were injected with NMBA 0.5mg/kg subcutaneously (s.c.) only, The rats in low dose treated group model were injected with a combination of NMBA 0.5 mg/kg(s.c) and triterpenes compound of Cortex Periplocae 10mg/kg intramuscularly (i.m.). The rats in low dose treated group model were injected with a combination of NMBA 0.5 mg/kg (s.c) and triterpenes compound of Cortex Periplocae 20mg/kg intramuscularly (i.m.). three times weekly for 5 weeks.2 The histophathologic changes were observed by light microscope.3 The expression of PCNA protein in esophago-epithelium of F344 rats was detected by immunohisto-chemistry .4 Effect of triterpenes compound of Cortex Periplocae on the proportion of CD4~+ and CD4~+CD25~+regulatory T cells NMBA -induced esophageal tumorigenesis in F344 rats, and the proportion was detected by FCM.5 The Effect of triterpenes compound of Cortex Periplocae on the levels of IL-10,IL-2 in peripheral blood of NMBA- induced esophageal tumorigenesis in F344 rats, and the levels were detected by ELISA.Results:1 General observations of F344 rats:The mean body weights and food consumption in all rats were not significantly different throughout the experiment. No observable gross or histopathologic changes occurred in the lungs, livers, kidneys.2 The formation of esophageal carcinomas was not observed in normal control group and soy oil control group throughout the experiment.After 9, 15 weeks of treatment.there are visible protrusion lesion in NMBA treated rats (18%), that is plosity or solitary. At week 25, visible esophageal tumorigenesis(≥1mm) occurred in model group(about 66.7%);after triterpene compound of Cortex Periplocae treatment At week 25, triterpene compound of Cortex Periplocae reduced the incidence of esophageal cancer from 20% in low dose treatment group to 33.3% in high-dose treatment group.this reduction was significant(p<0.05).3 There are few number of inflammatory cells in esophageal mucosal epithelial cell layer of normal control group rats, and no other abnormal performance occurred, while there are changes of organizations in the model group rats esophageal epithelium, which are hyperplasia and papillary hyperplasia.4 Immunohistochemistry showed there were different degrees of PCNA positive cell in esophageal epithelial tissue of each group.The expression of PCNA in model group was increased with time-dependent manner. the PCNA-positive cell index in model group (9, 15 and 25 weeks) were 213.17±29.74, 268.35±39.56, 327.24±28.1. Statistical analysis showed that the PCNA-positive cell index in model group was higher than the PCNA-positive cell index in the normal control group (p<0.05). The PCNA-positive cell index in high doses treated group and low dose treated group were significantly decreased (p<0.05), compared with model group.5 FCM showed that after the NMBA treatment 9 weeks, CD4~+ T cells in peripheral blood of model group rats were decreased significantly and CD4~+CD25~+ regulatory T cells in peripheral blood of model group rats were significantly increased, which deteriorated further with the time going on (p<0.05). After triterpenes compound of Cortex Periplocae treatment at weeks 9,15, the proportions of CD4~+CD25~+ regulatory T cells were decreased, the proportions of CD4~+ cells were significantly increased (p<0.05),compared with model group.6 ELISA showed that after the NMBA treatment 9 weeks, the levels of IL-10 in peripheral blood of NMBA-induced esophageal tumorigenesis in F344 rats were significantly higher than those in normal control group and soy control group. After triterpenes compound of Cortex Periplocae treatment 9,15weeks, the levels of IL-10 in peripheral blood of rats were decreased significantly,compared with model group.7 ELISA showed that the levels of IL-2 in peripheral blood of NMBA-induced esophageal tumorigenesis in F344 rats were significantly lower than those in normal control group and soy oil control group, after the NMBA treatment 9 weeks.And After triterpenes compound of Cortex Periplocae treatment 9, 15 weeks, the levels of IL-2 in peripheral blood of rats were increased significantly, compared with the model group.Conclusions:1 The incidence of esophageal tumors was significantly reduced by Triterpenes compound of Cortex Periplocae in high dose treated group and low dose treated group.2 The expression of PCNA proteion was increased in model group with time dependent.3 After triterpenes compound of Cortex Periplocae treatment, the proportions of CD4~+CD25~+ regulatory T cells in peripheral blood of rat were decreased, and the proportions of CD4~+ cells were increased significantly.4 After triterpenes compound of Cortex Periplocae treatment. the expression of IL-10 in peripheral blood of rats was decreased, while the expression of IL-2 in peripheral blood of rats was increased.
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