Investigation On Drug-regulated Homeostasis

Objective: In this part of study, we tried to investigate the regularity of in vivo and ex vivo gastrointestinal smooth muscle's bidirectional regulation produced from the combination of inhibitory and stimulatory drugs.Methods: Three pairs of inhibitory and stimulatory drugs, i.e., atropine and domperidone, isoprenaline and neostigmine, aminophylline and acetylcholine were used in the study. Three levels of indexes were used, i.e, in vivo, ex vivo, and in vitro studies. In the in vivo assay, we used intragastric administration and intraperitoneal injection combined with perfusion of carbon paste to observe the gastric emptying rate and the small intestinal propulsion rate. In the ex vivo assay, we used the contractility of gastrointestinal smooth muscle strip as the index to observe the effect of concurrent use of drugs on the contraction of smooth muscle. In the in vitro assay, we observed the influence of drug on myosin phosphorylation.Result:(1)In the in vivo assay, the three pairs of inhibitory and stimulatory drugs used concurrently inhibited the gastric emptying rate and the small intestinal propulsion rate of mice gastrointestinal in relative high contraction state which was induced by carbachol and enhance the the gastric emptying rate and the small intestinal propulsion rate of mice gastrointestinal in relative low contraction state which was induced by adrenaline;(2)In the ex vivo assay, the three pairs of inhibitory and stimulatory drugs used concurrently inhibited the contraction of rat gastrointestinal smooth muscle in relative high contraction state and enhance the contraction of rat gastrointestinal smooth muscle in relative low contraction state regardless of use carbachol or adrenalin to make the model;(3)In the in vitro assay, atropine,isoprenaline and aminophylline inhibited the Ca²⁺ dependent phosphorylation of smooth muscle myosin respectively; and domperidone,neostigmine and acetylcholine enhanced the Ca²⁺ dependent phosphorylation of smooth muscle myosin regardless of change the concentration of MLCK. The three pairs of inhibitory and stimulatory drugs used concurrently inhibited the Ca²⁺ dependent phosphorylation of smooth muscle myosin in relative high contraction(MLCK in high concentration) and enhanced the Ca²⁺ dependent phosphorylation of smooth muscle myosin in relative low contraction(MLCK in low concentration).Conclusion: The three pairs of inhibitory and stimulatory drugs used concurrently produced bidirectional regulation on the in vivo gastrointestinal movement, ex vivo gastrointestinal smooth muscle contractility, and phosphorylation of myosin.We suppose that the mechanism of bidirectional regulation is concerned with the Ca²⁺ dependent phosphorylation of myosin. Objective:In this part of research we use the anti-aging experiment of mice to investigate the influence of drug with multiple factors to the organism counterbalance of mice.The factors we used including drug,administration mode,administration dosage and food restrain.We want to know whether these factors can prolong the mice lifespan and improve its survival state.Method:We want to know whether the factors we used including drug,administration mode,administration dosage and food restrain can prolong the mice lifespan and improve its survival state.The drugs we used including ginseng,medlar,mulberry and desertliving cistanche herb.We determine two parts of index of mice,the first part is the lifespan of mice,in another part we use the liver,brain and blood serum of mice to determince some aging index including SOD,MDA, GSH-PX and TG.Result:This research can prolong the lifespan of mice significantly,the disparity of control group and administration groups was significant but the disparity between the administration groups was not significant.The disparity of SOD,TG and GSH-PX value among control group and administration groups are significant but the MDA value is not. The disparity of SOD,MDA,GSH-PX and TG value between administration groups are all not significant.Conclusion:We can prolong the lifespan of mice and improve its survival state significantly by administration,the disparity of the biochemical indicator among control group and administration groups is significant but the disparity between administration groups are not significant.We suppose the reason is that the concentration of drug is too low.