| Objective: To investigate or observe the influence ofα-ketoacid(sα-KA) on the anemia of SD rats caused by the 5 / 6 nephrectomy, meanwhile to explore its possible mechanism, so as to provide evidence for the clinical treatment of renal anemia caused by chronic renal disease basing on animal experiments and expand the clinical thinking.Methods: 37 male SPF grade Sprague-Dawley rats were randomly divided into 2 groups, sham operation group (9 rats) opened the peritoneal cavity only stripped the envelope at the same time retained the adrenal gland but not to removed the kidneys , and the remaining 28 rats underwent 5 / 6 nephrectomy in two steps to produce the model of chronic renal failure, 3 months later testing the renal function , the successful model of the 19 rats were stochasticly divided into the treatment group (10 rats) and the model group (9 rats) , the treatment group were administrated with theα-ketoacids (0.5g/300g*day)dissolved in 5ml normal saline,the other two groups were given equal normal saline . 2 months later all the rats were collected blood by puncture the angular vein to test HGB, RBC, HCT and other blood analysis testing, and centrifuged the blood for the supernatant to detect creatinine(Scr), urea nitrogen (BUN), and the consistency of serum Angiotensin-Ⅱ(Ang-Ⅱ); one part of remnant kidney tissue fixed in Bouins Liquids were made for the PAS and Masson stain to observe Histological and pathological changes and immunohistochemical performed to examine the expression of a-smooth muscle actin(α-SMA) in renal tissue;the rest part was made into the homogenate supernatant to detect the concentration of renal tissue Erythropoietin (EPO).Results: 1: Compared with the sham operation group, the HGB, RBC, HCT in treatment group were significantly decrease (P <0.01); But compared with the model group, treatment group HGB, HCT and RBC were significantly increase (P <0.05 ). 2: Compared with the sham operation group, treatment group have a higher BUN and Scr, there is significant differences (P <0.01); Compared with model group, the BUN in treatment group was significant lower (P <0.05), and the Scr in treatment group also lower than the model group (P <0.05). 3: Compared with treatment group and model group, sham operation group has significantly higher concentration of EPO in renal tissue (P <0.01); But compared with the model group, the concentration of EPO in the treatment group were significantly higher (P<0.05). 4: the Masson stain showed there are diffuse mesangial proliferative glomerulonephritis in glomerular accompany with segmental aggravating, resemble FSGS lesions, a small number of glomerular capillary loop existing some micro-thrombosis seemed to be ischemic shrinkage, partial glomerulars seemed to be hypertrophy for compensatory; a few tubular epithelial cells flattened, brush border lost, bare basement membrane formed, accompany with tubular atrophy and expansion, a large number of protein casts formed in the tubular;there are lots of mononuclear and lymphocyte cells infiltration in the renal interstitium ,accompany with focal or segmental fibrosis in model group; compared with the model group,the treatment group also exists such analogous Pathological changes as the expansion and atrophy of tubular, interstitial inflammatory cell infiltration and focal fibrosis formation, but not so serious than model group. Sham group had no significant pathological changes in renal tissue. 5: Compared with treatment group and model group, sham operation group has significantly lower consistency of Ang-Ⅱ(P <0.01); between treatment group and model group, the consistency of Ang-Ⅱshowed no significant difference (P> 0.05). 6: Compared with sham operation group, the expression ofα-SMA will significantly increased in model group and treatment group, which appeared to be see around the tubular and renal interstitium, but compared with model group there is less expression in the treatment group; the sham group has no obvious expression except strong expression around the vascular.Conclusion:α-KA can both improve the anemia index of RBC HGB and HCT caused by CKD and the concentration of EPO in renal tissue ,the possible mechanisms may be as follows①α-KA can protect the rest renal function (RRF) that indirectly increases the amount of EPO secretion in renal tissue by reducing the excretion of urinary protein and delaying renal intestitium fibrosis;②α-KA can improve the branch-chain amino acid metabolism and maintain good and steady nutritional status, in which red blood cells and hemoglobin can synthesize quickly;③α-KA can improve the metabolism of calcium and phosphorus, decrease serum PTH , thereby reducing EPO resistance;④α-KA can improve the micro-inflammatory state in the body, which is benefit for improving the response of EPO;⑤α-KA can transform the waste of urea nitrogen in the body, thus easing the state of acidosis, further improving the living environment of red blood cells.⑥but there is no evedence proved thatα-KA can diretly promote the secretion of EPO,it needs more further experments. |
PDF Full Text Request