| Decoted from "Treatise on Exogenous Febrile Disease", Zhen Wu Tonga is composed of aconite, ginger, Poria, Atractylodes, white peony root, which is a prima facie evidence of excessive sweat injury Yang, Yang Shao disease syndromes and set the pan of water in the name of party. Later in the treatment of various yin yang, water and gas overflows the card, the effect is significant[1]. Mainly to improve myocardial contractility, improve oxygen supply ischemic myocardium, increase urine output, lower creatinine, urea nitrogen and so on. Clinical reports [2]:Zhenwu Tonga with Salvia, safflower, etc., can treat congestive heart failure, compared with the cardiac diuretic in the same period, the prescription could improved the heart and kidney function significantly and the side of the internal environment, such as sodium, potassium, chloride, plasma osmolality, blood glucose, blood urea nitrogen, blood pH did not change significantly. The interference of prescription to the body of environment is very small. Because of the boiling process of Zhen Wu Tang is quite complicated, and the patients taking inconvenient,so a pharmaceutical company change the dosage form into a capsule. The task Force in accordance with the drug technology requirements of "Drug Registration", make preclinical pharmacodynamic assessment and safety evaluation to the Zhenwu capsules. One of the topic for the content of the project of preclinical is pharmacodynamic evaluation.Objective:Study on the effect Wenyang respectively Zhenwu capsule powder to dexamethasone-induced deficiency in male mice KM model; give the rat intraperitoneal injection with the same species renal cortex suspension; copy active Heymann nephritis model, give different doses Zhenwu capsule powder, study the role of drugs on active Heymann nephritis model and preliminary study mechanisms; give different doses of Zhenwu capsule powder to SPF SD rats, observe and measure the urine after administration 6h and the Na+, K+, Cl- concentration in urine,observe the diuresis of Zhenwu capsule powder on rats and preliminary explore the mechanism.Method:1. Wenyang test of Zhenwu capsule powder to KM dexamethasone-induced deficiency of male mice. Using intramuscular injection of dexamethasone sodium phosphate injection to copy deficiency model,analyze the animal rectal temperature, locomotor activity, the impact of swimming time and the levels influence to the leukocytes (WBC), red blood cell (RBC), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP). Take the pituitary, adrenal, gonadal, the liver, spleen, thymus, evaluate the organ coefficient, calculated the role of Yang Zhenwu capsule.2. Diuretic action of Zhenwu capsule in rats. Using an intragastric administration of 1% saline water load in rats, analyze the effects of different concentrations of Zhenwu capsule suspension for six hours urine of rats, and on urine PH value and Na+, K+, Cl- concentration to evaluate the diuretic effect Zhenwu capsule on rats.3. Effect of treatment of Zhenwu capsule powder on active Heymann nephritis rat Cortex suspensions prepared first according to the literature method by rat kidney and Freund’s adjuvant, and then intraperitoneal injection once every two weeks, copy active Heymann nephritis models. Urinary protein model to be displayed, then the successful model of the 50 rats were randomly divided into five groups:model group (0.05g CMC-Na/kg), low-dose group Zhenwu capsule (5g crude drug/kg), Zhenwu capsule dose group (lOg crude drug/kg), high-dose group Zhenwu capsules (20g crude drug/kg), positive control group (tripterygium,11mg/kg), which were administered these drugs a month. By observing body weight of rats before and after administration, general condition, urine protein content, measured abdominal aortic blood urea nitrogen and serum creatinine, total protein, albumin content, anatomical organ coefficient is calculated to take the kidney and renal pathology and studies, to research Zhenwu capsule powder therapeutic effect of active Heymann nephritis rats.Results:1. Compared with the vehicle control group, the mice in the model control group gained weight significantly slower, their independent activities also reduced, swimming time was significantly shortened, and significantly lower cAMP levels in the blood, and cGMP content was significantly increased. And model control group compared to Zhenwu capsule powder, the growth differential weight high dose group and positive control group of mice was significantly, significantly increased locomotor activity, swimming time was significantly longer, and significantly elevated blood cAMP levels, and cGMP content was significantly reduced, and has no significant difference compared to the control group and the vehicle; histopathological examination showed positive drug and in high doses Zhenwu capsule powder can significantly improve the deficiency caused by the adrenal gland, testis, spleen, thymus and pathological conditions function, improve immune function in mice. Description Zhenwu capsule powder, deficiency of dexamethasone-induced high-dose group and positive control group had a good Wenyang role2. Compared with the vehicle control group, positive control group and Zhenwu capsule powder high dose group was significantly increased urine volume. Compared with the vehicle control group, positive control group after administration 3h,5h significant increase in urine output; Zhenwu capsule powder high dose group at 4h, 5h,6h urine were significantly increased; Zhenwu capsules at a dose of powder after drug 5h,6h urine increased significantly; Zhenwu capsule powder high dose group urine Na+ total increased significantly in 1h high Zhenwu capsule powder, middle dose group and positive control group Na+ content increased significantly; positive drug the control group significantly increased urinary K+ total. Positive control group at 1h,2h urinary K+ content increased significantly, Zhenwu capsule powder high-dose group was significantly increased at 2h urine K+; animals in each group showed no significant change at each time point total and urine Cl-.3. Compared (ie, administration of the vehicle control group)with normal control group, model group rats significantly increased urinary protein, weight gain slowed down, suggesting that made a successful model. Interim administration, compared with the model group, Zhenwu capsule pink high-dose group and positive control group, urinary protein levels were significantly lower (P<0.05); administration month later, compared with the model group, high Zhenwu capsule powder, were significantly lower in the low dose group and positive control group, urinary protein levels (P<0.01); test results serum biochemical indicators show Zhenwu capsule powder of high-dose and positive control group, serum creatinine levels were significantly lower (P<0.05), Zhenwu capsule powder high, were significantly lower in the low dose group and positive control group, blood urea nitrogen in water (P <0.01), Zhenwu capsule powder high dose group and positive control group, the total protein levels were significantly increased (P<0.05), Zhenwu capsule powder high dose group and positive control group albumin levels were significantly increased (P <0.05), each administered group of white/ball ratio no significant change.Pathology results showed, HE staining found in rat kidney tissue vehicle control group without degeneration, necrosis, no glomerular shrinkage, occlusion and tubular dilatation, interstitial edema, no inflammatory cell infiltration. Most kidney glomerular was significantly swollen, glomerular capillary plexus cells increased significantly, mainly an increase in endothelial cells, capillary wall thickening, glomerular shrinkage, occlusion, tubular appeared widely injury, edema, expansion or contraction in model group. Positive control group, Zhenwu capsule powder high dose group significantly improved kidney disease, glomerular endothelial cell proliferation was not obvious, cloudy swelling of the renal tubular epithelial cells reduced, no tubule lumen stenosis, glomerular number of lesions was significantly reduced. Zhenwu capsule powder, low-dose group glomerular lesions also improved, but the effect is not as good as positive control group and Zhenwu capsule powder high dose group. After six ammonia silver staining found no vehicle control group of rats glomerular basement membrane, a large number of model group diffuse thickening of the glomerular basement membrane. Positive control group, Zhenwu capsule powder and high dose groups and no or slight thickening of the glomerular basement membrane, in the low-dose group compared with the glomerular basement membrane positive control group, Zhenwu thick capsule pink high-dose group, and the model control group also improved.Conclusion:Zhenwu capsule powder, high dose group dexamethasone-induced deficiency of good Wenyang role, have a therapeutic effect to active Heymann nephritis rats, can significantly improve renal function, reduce basement membrane thickening pathological changes, the effect has no significant dose dependent. Zhenwu capsule powder high dose group and Jinkuishenqiwan group of SD rats were water load diuresis; diuretic effect Zhen Wu Tonga powder capsules appeared later than Jinkuishenqiwan group, but the diuretic effect is more durable; Zhenwu capsules diuresis powder may be through the promoted excretion of Na+ of urine to achieve. |
PDF Full Text Request