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We have reported that tumor necrosis factor-α (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by d-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring short hairpin RNA against the protein kinase C-α ( PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP 3 R1) expression in renal tissue were assessed. The effects of PKC-α silencing on TNF-α-induced IP 3 R1, specificity protein 1 (SP-1), and c-Jun NH 2 -terminal kinase (JNK) expression, as well as cytosolic calcium content were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-α. Renal IP 3 R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC-α. The PKC-α silence significantly improved the compromised GFR, reduced Cr levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. TNF-α treatment increased expression of PKC-α, IP 3 R1, specificity protein 1 (SP-1), JNK, and p-JNK in GMCs and increased Ca 2 + release and binding activity of SP-1 to the IP 3 R1 promoter. These effects were blocked by transfection of siRNA against the PKC-α gene, and the PKC-α gene silence also restored cytosolic Ca 2+ concentration. RNAi targeting PKC-α inhibited TNF-α-induced IP 3 R1 overexpression and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats.

Objective: To investigate the relation between serum level of interleukin-8 (IL-8), nitrogen monoxide (NO) and Helicobacter pylori (HP) infection, as well as the possible molecular mechanism of HP infection causing the imbalance of apoptosis and proliferation in gastric epithelial cells, which may lead to oncogenesis in stomach., Methods: Serum IL-8 level was detected with enzyme-linked immunosorbent assay (ELISA). Serum NO was detected with chrome reduction method using plated copper., Results: Serum level of IL-8 were 22.50 +/- 1.87 pg/ml in the normal tissue, 34.99 +/- 7.89 pg/ml in superficial gastritis, 65.27 +/- 10.60 pg/ml in atrophic gastritis and 94.84 +/- 11.09 pg/ml in gastric cancer (P < 0.01). Serum level of NO in the atrophic gastritis group (39.93 +/- 5.43 micromol/L) was significantly higher than that in the gastric cancer group (37.02 +/- 4.13 micromol/L) (P < 0.05). The differences in the other groups were not significant. IL-8 and NO levels in the HP(+) group were significantly higher than those in the HP(-) group (77.30 +/- 20.92 pg/ml vs 39.16 +/- 14.40 pg/ml, P < 0.01; 39.77 +/- 5.57 micromol/L vs 35.35 +/- 5.24 micromol/L, P < 0.01). Serum levels of IL-8 and NO in the cytotoxin-associated gene A protein (CagA)(+)HP group were significantly higher than those in the CagA(-)HP group (83.45 +/- 16.92 pg/ml vs 66.24 +/- 23.21 pg/ml, P < 0.01; 40.97 +/- 4.59 micromol/L vs 37.62 +/- 6.58 micromol/L, P < 0.05). Serum levels of IL-8 and NO showed positive correlation between superficial gastritis and atrophic gastritis groups (r = 0.881, r = 0.995), whereas no correlation was found in the normal or gastric cancer groups., Conclusion: Serum levels of IL-8 and NO are correlated with CagA(+)HP strain infection. Combined detection of serum level of IL-8, NO and HP-CagA will contribute to the early diagnosis of precancerous lesion in the stomach.