ABSTRACT
Objective To determine the protective role of keratinocyte growth factor 2 (KGF-2) on dextran sodium sulfate (DSS)-induced murine colitis and investigate the mechanism of its effect on intestinal mucosal barrier.Methods A total of 36 male C57BL/c mice were divided into 4 groups:normal control group,DSS model group,model + KGF-2 (5 mg/kg) group and model + KGF-2 (10 mg/kg)group.Groups except the control were added 3.5 ％ DSS in drinking water.Disease activity index (DAD,weight change,colon length loss and histological score were detected to evaluate the protective effect of KGF-2 on colitis.Serum fluorescein isothiocyanate-dextran (FITC-D) permeability were assayed by multiscan spectrum.In order to explore the protective role of KGF-2 on murine intestinal mucosal barrier,ZO-1 and occludin protein concentration were detected by immunohistochemical staining and Western blot.Meanwhile,cytokines including TNF-α,IL-6,IL-10,TGF-1β,IFN-γ and IL-1β in colonictissue were detected by ELISA.Results Compared with DSS-induced colitis model group,10 mg/kg KGF-2 significantly reduced DAI (P =0.021 1),weight loss (P =0.017 6),colon length loss (4.956 ±0.2583 vs.6.289±0.215 7,P =0.001 1),histologicalscore (12.17±1.222 vs.7.000±0.6325,P =0.001 1),and FITC-D permeability (168.5 ± 27.01 vs.14.62 ± 1.812,P =0.004 7) and reversed the downregulation of tight junction (TJ) proteins (ZO-1:0.158 6 ± 0.010 51 vs.0.387 9 ± 0.028 64,P＜0.000 1;occluding:0.300 5 ± 0.026 56 vs.0.445 0 ± 0.056 62,P =0.043 4).Significant decrease of TNF-α (68.93 ± 3.379 vs.40.41 ± 1.576,P＜0.000 1) and increase of IL-6 (3 755 ± 309.8 vs.5 640 ± 418.0,P =0.004 7) and IL-10 (304.0 ± 21.47 vs.521.2 ± 49.40,P =0.002 4) levels were noted in the 10 mg/kg KGF-2 treated mice.The effect of the KGF-2 was dose-dependent.Conclusions KGF-2 could ameliorate DSS-induced colitis and it may be associated with the decrease of the damage of mucosal barrier structure and funcntion by preventing ZO-1 and occludin from downregulating.The protective effect of KGF-2 on intestinal barrier function may also be exerted by inhibition of TNF-α and stimulation of IL-6 and IL-10 secretion.
ABSTRACT
Atherosclerotic cardiovascular diseases(ASCVD)are the major causes of morbidity and mortality worldwide. Previous randomized controlled trials confirm that statin therapy can effectively reduce the level of low density lipoprotein cholesterol(LDL-C),all-cause and cardiovascular disease mortality in patients with and without ASCVD.However,there is no widespread use of lipid-lowering therapy to achieve the benefit in high risk patients with ASCVD and patients without ASCVD. Therefore, it is necessary to further elaborate the clinical benefits of statins and their combined use for lipid regulating therapy and increasing the beneficiaries.