Primary Animal Experimental Study Of The Role Of Mitochondria In Damage Of Kidney And Other Organs In CRF And Soluble Granules Yishenjiangzhuo Therapy

Objectives: To observe the renal pathology and function, the level of MDA and SOD in plasma, and the super-microstructure of kidney, heart and small intestine in 5/6 nephrectomy rats of chronic renal failure (CRF) model, in order to study the theories of "High Metabolism in Renal Tubules" and "the Diseases Due to Uremic Toxins" in CRF. To investigate the effect of Soluble Granules Yishenjiangzhuo therapy, and to study the mechanism of "Strengthening Earth to Restrain Water" according to the theory of "the Mitochondrion is the Essence of the Spleen In Five Zang In TCM".Materials and Methods: 40 Sprague-Dawley Rats (SD Rats) were divided into five groups at random. 8 rats served as normal control group. The remaining rats were given 5/6 subtotal nephrectomies to establish the model of CRF. One month after nephrectomy the model of CRF rats were subdivided into 4 groups randomly: the model control group, the Chinese Rhubarb group, the large dose and the small dose of Soluble Granules Yishenjiangzhuo. The animals of large dose received oral administration of Soluble Granules Yishenjiangzhuo in a dose of 20.0 kg-1d-1 for two months, the small in a dose of 10.0 kg-1d-1, and the Chinese Rhubarb were given Granules of Chinese Rhubarb a dose of 0.21 kg-1d-1 (equal to its raw material of a dose of 0.5 kg-1d-1) in the same time. All the drugs above were dissolved by 2.5ml distilled water. The normal control group and the model control group were given the same cubage distilled water.Results: (1) The difference of BUN, Scr, MDA SOD and the score of glomerulus/tubules pathology is significant between the model control group and the Chinese Rhubarb group/the large/small dose of Soluble Granules Yishenjiangzhuo group (P<0.01 or P<0.05), and between the Chinese Rhubarb group and the large/small dose of Soluble Granules Yishenjiangzhuo group (P<0.01 or P<0.05). (2) The analysis of correlation showedthat the BUN and Scr level was positively correlated to that of MDA, (r=0.715, 0.789, P<0.01,0.01), negatively correlated to that of SOD (r=-0.719, -0.810, P<0.01,0.01). (3) The variations of renal super-microstructures was the same as its pathology, the damage of mitochondria is the most serious, that of the Chinese Rhubarb is the secondly most serious, that of the large/small dose of Soluble Granules Yishenjiangzhuo is the slightest in all. (4) The effect of super-microstructures variations of heart and small intestine are the same as kidney.Conclusion: (1) The CRF model of 5/6 nephrectomy rats is a model of high metabolism in renal tubules. (2) The mechanism of high metabolism in renal tubules is the mitochondria over-working. (3) In CRF, uremic toxins injured cell by influencing mitochondria. (4) It's "Water Retention Due to Spleen Deficiency" that the uremic toxins damage cell by influencing mitochondria. (5) The main therapy principle of the Soluble Granules Yishenjiangzhuo is "Strengthening Earth to Restrain Water". It not only protect over-working mitochondria, but also improve the ability to resisting uremic toxins to decrease the syndrome of "the Disturbance of Spleen Due to Damp-pathogen".