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Objective To investigate the activation of NF-κB and regulation by ubiquitin (Ub)-proteasome pathway in the aorta of rats with chronic renal failure(CRF).Methods The CRF rat model was established by right nephreetomy and left branch renal artery ligation.The CRF rats were were randomly divided into simple CRF group(n=20)and CRF+M used as control group(CON).The NF-κB and the Ub mRNA expression were detected by RT-PCR,and its protein expression was analyzed by immunohistochemistry method.The activity of NF-κBwas mesured by EMSA method.The concentration of IL-1 and TNF-α was detected by ELISA.Results Compared with the CON group,the concentration of serum IL-1 and TNF-α was increased significantly in CRF group [IL-1:(9.02±1.29) vs (2.74±0.96)mg/L,P＜0.01;TNF-α:(50.02±9.52) vs (14.04±1.29)mg/L,P＜0.01]at month 4 after operation.The mRNA expression of NF-κB and Ub in the aorta of CRF group was 1.38 and 1.29 times as that of CON group(P＜0.01).and the protein expression of NF-κB and Ub was 3.75 and 20.5 times as that of CON group(P＜0.01).Compared with the CON group,the activity of NF-κB in the aorta of rats of CRF group was elevated markedly at month 4 after operation(P＜0.01).All the indices were further increased at month 6 after operation.Compared with CRF group,the concentrations of serum IL-1and TNF-α were decreased significantly in CRF+M group[IL-1:(2.94±0.33)mg/L,P＜0.01;TNF-α:(12.80±2.12)mg/L,P＜0.01].The mRNA and protein expression of NF-κB and Ub were also decreased markedly(P＜0.01),and the activity of NF-κB was decreased significantly at month 4 to 6 after operation(P＜0.01).But the amount of ubiquitnative protein was increased significantly in the aorta of CRF+M group as compared to CRF group(P＜0.01). Conclusion The inflammatory signal pathway of ubquitin-proteasome-NF-κB pathway was activated in the aorta of CRF rats,and the proteasome was probablely an important pharmacological intervention target to regulate the activation of NF-κB.
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Objective To observe P27 expression and proliferation of mesangial cells of rats with Thy1 glomerulonephritis and to evaluate the interfering effect of valsartan, a specific angiotensin Ⅱ receptor antagonist, on Thy1 glomerulonephritis. Methods Rats were divided into normal control group, Thy1 glomerulonephritis group and valsartan treatment group. Following the onset of glomerulonephritis, renal morphological changes were observed on days 1, 3, 5 and 7, and proliferating cell nuclear antigen(PCNA) and P27 expression in glomerulus were measured by immunohistochemistry and Western blotting. Results High expression of P27 was found in quiescent mesangial cells of normal rats, but decreased expression in mesangial cells of rats with Thy1 glomerulonephritis, accompanying with the proliferation of mesangial cells. In valsartan treatment group, glomerular hypercellularity, mesangial matrix expansion and PCNA expression were significantly reduced as compared with those of the untreated rats with Thy1 glomerulonephritis from day 3 to day 7( P
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The authors analyzed the current problems about clinical postgraduate cultivation in the medical colleges or institutes or hospitals in China,and proposed some solving ideas for discussion,including raising the applicative qualification for enrolling postgraduate,reinforcing construction of the soft and hardware condition,guaranteeing enrolling number of postgraduate for key colleges and institutes.
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Objective To retrospectively analyze the clinical characteristics of acute renal failure ( ARF) induced by crush syndrome after Wenchuan earthquake,and summarize the rational and effective treatment managements of this kind of ARF. Methods The case histories of 12 patients diagnosed as ARF related to the crush syndrome in Wenchuan earthquake were pigeonholed. In order to evaluate the curative effects of the clinical features,laboratorial examination,continuous renal replacement therapy ( CRRT) and cure time were ana- lyzed. Results Anaemia,fever and lung infection were frequently happened in the patients diagnosed as ARF,and the frequency was 91. 67% ,66. 67% and 58. 33% respectively. Pleural effusion and acute respiratory distress syndrome ( ARDS) were noted in 41. 67% of the patients,and the increase of transaminase was noted as 91. 67% . Hypocalcaemia,hypoproteinemia and marked increase of creatine kinase ( CK) appeared in all patients. The patients with CK value exceeded 3 000 IU/L were received CRRT,and there was marked relativity between these 2 variables ( r =0. 845) for the treatment of ARF. Although the proportion of CRRT practiced highly in patients with oliguria,fasciotomies and amputations,there was no significant difference when compared with closed injury and non-oliguria patients ( P = 0. 522 7) . Compared with patients without infections,wound infections were obviously delayed the cure time of ARF ( P = 0. 025 5) . Conclusion As compared with ARF from other causes,ARF related to the crush syndrome has unique characteristics,and easily complicates with multiple organ dysfunction syndrome. Among the treatments, heteropathy and renalreplacement therapy are frequently used. Thorough debridement and infection control are beneficial to renal function recovery.
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To evaluate the effects of interleukin-1 and interleukin-4 on the expression of p27 (one of the negative cell-cycle proteins) and CDK 2 (cell-cycle depending kinase, one of the positive cell-cycle proteins) on renal mesangial cells of rat in vitro, and to analyze their significance. The results showed that the proliferation of mesangial cells was induced markedly by interleukin-1, while the expression of p27 was down-regulated and that of CDK 2 was up-regulated. All of above changes were prevented by interleukin-4. The results suggested that the responses of rat renal mesangial cells to interleukin-1 and interleukin-4 were closely related to the changes in the expression of p27 and CDK 2.
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AIM: To investigate the characteristics of pathological injury and its relationship with the transformation of energy metabolism of hypertrophic cardiomyocytes after hypoxia-reoxygenation. METHODS: Cultured rat cardiomyocytes were induced to be hypertrophy by angiotensin Ⅱ (Ang Ⅱ) and norepinephrine (NE). Glucose oxidation rate (GOR), glucolysis rate (GLR) and fatty acid oxidation rate (FOR) were determined by liquid scintillation counting, and cell apoptosis was detected by TUNEL. RESULTS: (1) Compared with the normal cardiomyocytes (NC), the GOR and GLR were slightly higher and the FOR was slightly lower in the group of hypertrophic cardiac cells (HC) than that in the group of normal cardiomyocytes cultured under the normal oxygen partial pressure. The apoptosis rate had no difference between the two groups. (2) The apoptosis rate of hypertrophic cardiomyocytes after hypoxia was significantly higher than that of hypertrophic cardiomyocytes in normal culture. It was higher and moreover, some necrosis cardiomyocytes appeared after reoxygenation. (3) GOR and FOR in both group (NC and HC) were slightly lower in a time-dependent manner after hypoxia than that in each group in normal culture condition. GLR had no difference in both group. The GOR was more lower in both NC and HC group when reoxygenation than that at the point of hypoxia for 2 hours, but the GLR and FOR were significantly higher in HC than that in NC when reoxygenation. (4) The GOR was significantly higher and the GLR and FOR were significantly lower in the hypertrophic cardiomyocytes group (HC) with dichloroacetate (DCA, 1 000 ?mol/L) or trimetazidine (TMZ, 1 ?mol/L) treated respectively than that in the responded hypertrophic cardiomyocytes after stimulation by hypoxia-reoxygenation. In the meanwhile, the apoptosis rate also was markedly lower in the treated hypertrophic cardiomyocytes group. CONCLUSION: The transformation of energetic metabolism pathway plays an important role in the pathogenesis (mainly the apoptosis) of the hypertrophic cardiomyocytes after hypoxia-reoxygenation.