Studies On The Toxic Target Organ Of CLZ And Related Mechanisms

[OBJECTIVE] To explore the sensitive organ of CLZ, and investigated the mechanisms of its efficacy.[METHODS] Firstly, to find the target organs of CLZ on the basis of the result of long-term toxicity test.Sencondly, to observe the impact of CLZ on the nerve.The effect of the thermal hyperalgesia was carried out through ache models induced by hot board methods and irradiation method of radiant heat in mice. The effect of CLZ on the A-δ fiber and C fiber in mice were measured by electrical stimulation procedure.And to observe the effect of CLZ on the motor nerve of rats by measuring the MSCN. Finally, to explore the effect of CLZ on the immune system by the test of DTH, then to investigate the effect of CLZ on NEIN by measured the levels of hormone secreting on the HPA.[RESULTS] The result of the long-term toxicity tests showed that the rats of CLZ6.0g/kg grew more slowly. The number of reticulocyte, levels of MCV, MCH, PDW reduced, and the level of RDW significantly increased, comparing with the control group (P<0.01); The levels of AST, ALT of the group of CLZ6.0g/kg increased significantly (P<0.01) while the ALB, A/G reduced. Some of the visceral organs index of the group of CLZ6.0g/kg were higher than the control group, such as the liver, the kidney,and the adrenal.On the contrary the spleen index and the thymus index were smaller than the control group(P<0.05).The results of pathological mechanism showed that the thymus atrophy, the salivary gland atrophy and the parotid gland atrophy happened in the sample of the dosage of6.0g/kg; meanwhile the muscle fiber necrosis and the bone marrow cells reducing. Morever, sperm stranded in the testis in the male annimal.The results of Electron Microscopy showed that The rat renal tubular cortex chromatin nucleus got together, the mitochondria swell and cristae disappeared. Glomerular epithelial cells swelling, endothelial nuclei chromosome gathering, Crest axon disappearing, Adrenal tubular mitochondria disappearing, lipid drops increasing were also observed. Finally,The sciatic nerve fiber demyelinated and the schwann cells reduced.The content of vitC in the adrenal rose significantly and the level of MSCN became lower after administrated CLZ12.0g/kg for7days in rats. The thermal hyperalgesia of mice went up after administrated CLZ for7days.Meanwhile,CLZ could rise the level of ACTH and CRH, but lower the level of Cortisol. [CONCLUSION] The target organs of CLZ were the liver, the kidney, the adrenal, the spleen and the thymus.CLZ had an effect on the the blood system, immune system, and nervous system. On the one hand, CLZ could reduce the level of heat pain threshold and slow down the rate of the MSCN. Perhaps that due to the number of schwann cells tailing off. On the other hand, CLZ can increase the rat adrenal index, its action mechanisms may relate with more CRH and ACTH, which causing adrenal cortical hyperplasia.The detailed mechanism need to be reseached more in future.