| It has been documented that SW has such functions as cytotoxicity, immunoregulation, cytoprotection, antiviral and antibacterial activities etc, which enables it to inhibite the metastasis and the spread of the tumor cells while to stimulate the apoptosis, which makes many researchers focus on it. It has been described that SW is an efficient and specific inhibitor of different kinds ofα-mannosidases, but which is inhibited most is not known. It is also not clear that whether SW has effects on the transcription, translation, processing and modification ofα-mannosidase. In this research, SW poisoning model was reconstructed in SD rats using Oxytropis kansuensis Bunge as the SW resourse, through the monitor of biochemical and antioxidant indexes and the histopathological and molecular biological researches, the subacute toxicity of SW towards SD rats and its effects on MAN2A1 and MAN2B1 at mRNA level were investigated. Furthermore the distribution and expression of MAN2A1 in different tissues of SD rats during the subacute O. kansuensis Bunge intoxication were investigated through immunohistochemical assay. The results are as below:1. Reconstruction of subacute O. kansuensis Bunge poisoning model in SD rats64 SD rats were divided into 4 groups (the control group and experimental groupⅠ,Ⅱ,Ⅲ), the dried plant of the Oxytropis kansuensis Bunge was comminuted, and different amounts of the grass powder (15%, 30% and 45% respectively, and the corresponding SW content was 0.03‰, 0.06‰, 0.09‰) were mixed with the feeds for the three experimental groups. After 77 days, The experimental groupⅢshowed typical clinical symptoms of loco disease.2. Effects of O. kansuensis Bunge on the hematologic and biochemical indicators in SD ratsThe results indicated that, after the poisoning, the values of RBC, MCV, RDW decreased. A time-effect as well as a dose-effect relationship was observed in GLU, CR, BUN, ALB, TG and ALT, and there was significant difference or extremely significant difference compared with the control group (P<0.05 or P<0.01), moreover the values increased with the experimental time extention.3. Effects of O. kansuensis Bunge on antioxidant indexes in SD ratsIt was observed that the levels of serum SOD and MDA reduced in SD rats after intaking O. kansuensis Bunge, while the CAT activity increased at first and then decreased. The SOD activity in the all four tissues of Experiment Groups rose in the initial stage, which decreased in the later stage in high-dose group. The CAT activity decreased at first and then increased with dose of intaking O. kansuensis Bunge rose and time extension in cerebrum, and livers'increased in Low-dose group. The difference of livers'MDA content was extremely significant between the Experiment Groups and the Control Group at the 35th day, and the kidneys'increased significantly in the later stage in Low-dose group.4. The pathological effects of O. kansuensis Bunge on SD ratsDuring the intoxication, there were comparatively large interspaces round the nerve cells in the Thalamus, Hypothalamus and Midbrain etc, which was dyed lighter compared with the normal ones by H-E staining. Purkinje cells, brainstem reticular formation, kidneys, liver and spleen appeared pathological changes with characterized vacuolar degeneration. the pathological changes in proximal convoluted tubule were more serious than thoses in distal convoluted tubule, moreover there were large amount of macrophagocytes in the splenic marginal zone.5. Effects of O. kansuensis Bunge on the expression ofα-mannosidase mRMA in SD ratsO. kansuensis Bunge inhibited the expression of cerebral and renal MAN2A1 mRNA, but the difference was not obvious in cerebrum (P>0.05). Low-dose O. kansuensis Bunge inhibited the expression of hepatic MAN2A1 mRNA while the high-dose one promoted it and the difference was extremely significant (P<0.01), which was opposite with that of spleen's, but the difference was not obvious in spleen (P>0.05). The expression of MAN2B1 mRNA decreased in the all four tissues, and the differences were not remarkable in cerebrum and spleen (P>0.05), whereras it was extremely significant in liver(P<0.01), and there was obvious difference in the kidneys in high-dose group (P<0.05).6. Effects of O. kansuensis Bunge on the distribution and expression of MAN2A1 in SD ratsIt was found that MAN2A1 expressed in all the areas but the cerebral molecular layer, Rad, Or and Mol in brain. The expression level of MAN2A1 positively correlated with the amount of the nerve cells and the granulocytes, in which MAN2A1 expressed more than other cells. The expression level of MAN2A1 was relatively higher in collecting tubule and distal convoluted tubule in kidneys, while there were no remarkable differences in hepatic and the splenic tissue. Moreover the expression level of MAN2A1 decreased with the increase of the poisonous dosage in cerebrum, cerebellum and kidneys, and the expression in some purkinje cells disappeared, which was inhibited significantly in liver in the Low-dose group. |
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