| Epidermal Growth Factor (EGF) can promote the differentiating and proliferating of cells from different tissues, and is also associated with the development and progress of cancers. Some studies showed that endogenous and exogenous EGF-stimulating drugs could play an important role in the effect of benign proliferation and reserving the atrophic gastric mucosa in Chronic Atrophic Gastritis (CAG). While other studies found there were overexpression and amplification of EGFR and its homogenous oncogene C-erbB2 in CAG with high atypical hyperplasic or intestinal metaplasia (II b). The EGFR would combine with high-level of EGF and take effect in the pathway of the oncogene express, breaking the normal self-regulate of cell cycle, and resulting in the development of cancer. Thus, there were risks of causing cancerous lesion when administratingEGF-stimulating drugs, such as gastric mucosa protection agents. So it is essential toidentify the efficiency and safety of using endogenous and exogenous EGF in experimental CAG. Our aim is to evaluate the safety of using these drugs by detecting the expression level of EGFR and oncogene C-erbB2 in rats of experimental CAG.Materials and Methods35 female Sprague-Dawley(SD) rats ,healthy, mature and weighing about 200 ?10g were adopted to our research, then randomized divided into four groups as follows: Group A (control group), rats fed with standard high-nutrient for 32 weeks; group B(CAG model group), in accordance with the method previously used by Si et al , rats were administered with 60% alcohol, 20 mmol/L sodium deoxycholate and 0.1% ammonia water for 24 weeks to establish CAG model, then continued to fed in standard normal condition for 8 weeks; group C (endogenous EGF-stimulator group), received AAG (Chinese traditional medicine ) 160mg/100g i.g once each day for 8 weeks after model establishment; group D(exogenous EGF group), rats were given EGF10μg/kg subcutaneous once every day for 8 weeks after model establishment. At the end of 32 weeks, all rats were anesthesia with 1% pentobarbital in foodless condition. 5ml blood was withdrawn from carotid artery through catheter. The level of serum EGF in rats were measured by radioimmunoassay in group A, B and C. Then all rats' stomachs were removed and opened along the greater curvature. Thegastric strip samples were cut along the lesser curvature and greater curvature, then immediately immersed in 10% buffered formalin and embedded in the paraffin. Paraffin sections were cut, mounted on glass slides, and stained with hematoxylin and eosin (HE), and with immunohistochemistry for EGFR and C-erbB2. We observed the pathologic change of gastric mucosa, and also detected the expression of C-erbB2 and EGFR. All the results were statistic by SPSS software.Results1. Pathological finding of gastric mucosaWe successfully established the experimental CAG. The typically pathological manifestation of CAG in group B were characterized as the decrease of the number of mucous glands, the thickness of myometrium, which extended toward lamina layer and inserted into the glands, and the infiltration and gathering of immense of inflammatory cell. But no intestinal metaplasia and atypical hyperplasia were observed. Compared with B group, there were significant improvement of pathological change in group C and D, and which were similar to the normal finding, such as the intimate arrangement of mucosa gland, the clear dividing line between gastric pit, the thinning of lamina propria and fewer infiltration of inflammatory cell. The results indicated that there were therapeutically effects of benign proliferation and reserving the atrophic gastric mucosa in CAG with exogenous EGF and endogenous EGF-stimulator agent.2. The level of serum EGF among groupsThe average level of serum EGF was 0.149 ± 0.0217 μ g/L and 0.608?.0208 μ g/L in group B and C respectively. Compared with 0.0395 ± 0.0164 μ g/L in group A , they were significant higher (P<0.05),(shown in table 1). Table 1 The level of serum EGF... |
