ABSTRACT
Objective To study the effect of curcumin on JAK2/STAT3 signaling pathway following ischemic cerebral injury in rats.Methods Sixty-eight SD rats were divided into sham opera tion group,cerebral ischemia group,curcumin treatment group and control group (17 in each group).After a rat focal cerebral hemmorrahge model was established,the changes of neurological behaviors in rats were recorded,expressions of TNF-α,IL-1β and IL-6 were detected by ELISA and those of JAK2,p-JAK2,STAT3,p-STAT3 and HMGB1 were detected by Western blot.Results The neurological behavior score was lower in curcumin treatment group than in cerebral ischemia group (1.53±0.62 vs 2.94±0.87,P＜0.05).No significant difference was found in expression levels of TNF-α,IL-1β and IL 6 between cerebral ischemia group and control group (P＞0.05).The expression levels of TNF α,IL 1β and IL 6 were lower in curcumin treatment group than in cerebral ischemia group (57.63±10.27 ng/L vs 99.35±8.97 ng/L,33.67 ± 9.10 ng/L vs58.43±7.22 ng/L,31.97±6.91 ng/L vs 49.23±6.28 ng/L,P＜0.01).The relative volume of p-JAK2/JAK2 and p-STAT3/STAT3 and the expression level of HMGB1 were lower in curcumin treatment group than in cerebral ischemia group (P＜0.05).Conclusion Curcumin can protect rats against cerebral injury following ischemia by inhibiting the JAK2/STAT3 signaling pathway and downregulating the HMGB1 expression,and can thus alleviate inflammatory reactions.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the intervention and mechanism of ambroxol combined with low-dose heparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with acute lung injury (ALI).</p><p><b>METHODS</b>Twenty-four healthy Japanese rabbits were randomly divided into three groups: (1) Normal saline control group (NC), (2) Oleic acid injury group (OA), (3) Ambroxol + low-dose heparin therapy group (AH). After the success of ALI model, AH group was injected ambroxol + low-dose heparin, while the NC group and OA group were injected the same dose of normal saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were determined. The pathological manifestation of both side lungs was observed at the end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate were tested. The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated. The pathological changes in lung tissue were observed by light microscopy, and the ultrastructural changes of lung tissue were observed by electron microscopy.</p><p><b>RESULTS</b>(1) The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group. (2) PaO2 was improved significantly in AH group, compared with that in OA group (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of MDA decreased significantly (P < 0.01), compared with those in OA group. (4) Except the content of IL-1beta in serum before treatment, the content of IL-1beta and TNF-alpha in serum, BALF, lung tissue homogenate of OA group increased significantly (P < 0.01), and those were obviously improved in AH group. (5) Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with that in OA group.</p><p><b>CONCLUSION</b>In ALI induced by OA, IL-1beta and TNF-alpha increases significantly and involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment of ALI.</p>