| It will be a promising assumption to develop a new artificial kidney. The kidney was the first organ whose function was substituted by an artificial device. The kidney was also the first organ to be successfully transplanted. Accordingly, the kidney will may be the first organ to be available as a tissue-engineered implantable device as a fully functional replacement part for the human body.With the development of blood purification in the past sixty years, renal substitution therapy with hemodialysis or hemofiltration has been an important life-sustaining technology. Whereas this therapy replaces the partial solute clearance function of the glomerulus but does not replace the transport, and metabolic and endocrinologic activities of the kidney, which are located predominantly in the tubular elements of the kidney. To optimize renal substitution therapy, a bioartificial renal tubule assist device (RAD) was developed, which is composed of renal proximal tubule cells grown within a hollow fiber cartridge. The addition of the tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely improve clinical outcomes,so we designed and carried out this study. Objective To establish a composite animal model with multiple organ dysfunction syndrome(MODS) and acute renal failure (ARF) and investigate the effect of treatment with a bioartificial kidney, which containing RAD, in animals with multiple organ failure and ARF, and its possible mechanism. So we can make the objective and scientific assessment for the RAD-treatment in ARF combined by MODS. Methods (1) Establishment of animal model Pigs were randomlydivided into two groups, one group received cecal ligation and puncture(CLP) plus bilateral ureteral ligation and another received sham operation. Vital signs, blood biochemical and arterial blood gas of animals were observed and recorded, which confirmed pigs to accord with diagnosis standard of ARF comnlicated bv MODS. (2)The treatment of RAD The pigs which were satisfied the criteria of MODS and ARF, were treated with RAD or sham RAD containing no cells or without any treatment within 24 hours. Blood biochemical markers including urea nitrogen and creatinine, and serum cytokines were recorded or measured and survival time of all the pigs was recorded. Serum IL-10 and TNF-a levels were determined by enzyme linked immunosorbent assay( ELISA). (3) Control group (1)Self-control in the course of the treatment with RAD; (2)Sham operation; (3)Sham RAD.Results 1: After operation the rectal temperature increased 4 hours later and the indexes enhanced 72 hours later, including SCr from 91.40+10.85umol/L to 995.25+125.28umol/L, BUN from 4.08+0.93 mmol/L to 48.80+1.41mmol/L, serum kalium from 3.81+0.57mmol/ L to 7.37+0.66mmol/L , ALT from 62.40+8.20u/L to 115.75+33.42u/L, AST from 53.00+14.85u/L to 278.00+96.20u/L and PaCO2 from 37.68+3.10 mmHg to 51.98+4.51mmHg (P<0.01), and the decrease of pH, from 7.38+0.04 to 7.25+0.05,P<0.05,and the value of MAP reduced from 160.20+18.58mmHg to 105.75+13.96mmHg, P<0.01. The mortality in the operative group is 100%, and the survival time was (74.96+23.00) hours, all the animals, however, survived in the sham-operative group. The essential pathological changes were obverved in several organs of the operative group under LM, whereas,there was no difference in the sham-operative group.Results 2: The peak level of IL-10 in the treatment with cell RAD were significantly higher(258.60+90.55 pg/ml) than the one in the treatment with sham RAD(126.55+9.69 pg/ml) or without any treatment (123.77 +28.54 pg/ml) (P=0.027). Afer the treatment, SCr from 869.00+104.52umol/L to 341.75+40.13 umol/L and BUN from 45.79+2.62 mmol/L to 14.19+1.55mmol/L in the RAD-treatment group,which reduction were more significant than those in sham- treatment group ( P<0.05 ), whereas the indexes increased in the group without any treatment. After the beginning of RAD-treatment, blo... |
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