p38 mitogen-activated protein kinase inhibitor suppresses the expression of pro-inflammatory cytokines in liver from brain dead rats / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the suppressive effect on the expression of pro-inflammatory cytokines in liver from brain dead (BD) rats through inhibition of p38 mitogen-activated protein kinase (MAPK) signaling pathway by SB203580.</p><p><b>METHODS</b>A total of 30 male Wistar rats weighing from 180 to 200 g were randomly divided into 3 experimental groups (1) BD group (n = 10) brain death was induced in rats; (2) BD+SB203580 group (n = 10) brain death was successfully induced and SB203580 (10 mg/kg) was given through dorsal vein of penis. After brain death artificial ventilation was maintained for 6 hours and only those with mean arterial blood pressure more than 80 mm Hg (1 mm Hg = 0.133 kPa) were accepted as BD donors. (3) Control group (n = 10) living healthy rats. The expressions of TNFalpha and IL-1beta mRNA in liver tissues were analyzed by RT-PCR and the protein expressions of TNFalpha, IL-1beta and phosphorylated p38MAPK were detected by Western blot.</p><p><b>RESULTS</b>The phosphorylated p38MAPK detected in the liver in BD group was significantly increased compared with the control group (q = 172.53, P < 0.01), and the expressions of TNFalpha and IL-1beta mRNA and proteins in liver were also significantly increased in BD group compared with the control group (q = 123.99, 135.35, 243.09 and 192.23, respectively, P < 0.01). The phosphorylated p38MAPK was decreased in BD+SB203580 group and significantly decreased compared with the BD group (q = 63.90, P is less than 0.05), but higher than that in control group (q = 108.63, P < 0.01). The expressions of TNFalpha and IL-1beta mRNA and proteins in liver were significantly decreased in BD+SB203580 group compared with the BD group (q = 55.11, 98.13, 61.03 and 50.85, respectively, P < 0.01), but higher than that in control group (q = 68.89, 37.22, 182.06 and 141.38, respectively, P < 0.01). SB203580 can suppress the expression of pro-inflammatory cytokines in the liver of brain dead rats through the inhibition of p38MAPK signaling pathway which may reduce the immunogenicity of donor livers.</p>