ABSTRACT
Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.
ABSTRACT
Objectives The purpose of this study is to observe the effects of valsartan on hepapetic fibrosis. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: valsartan -prevetive group (A), modle group of hepatic fibrosis (B)and valsar-tan-treating group (C). The model of hepatic fibrosis in rats was induced by intraperitoneai injection of dimethylnitrosamine (DMN) for 4 weeks(2ml/kg everyday, three times a week). Valsartan (10mg/kg everyday) was given together with injection of DMN per intrngastric (Ig) in group A for 8 weeks. After stop injection of DMN, the S valsartan(10mg/kg, everyday)was given per Ig in group C for 4 weeks. After modeling, normal saline were given per Ig everyday in group B. At the end of eighth week, the histomorphylogic structure of the liver was ob-served with light microscope. Immunohistoebemical staining was used to evaluate the expression of a-SMA. Results In group B, there was a large necrotic area and a number of pesudolobes appeared in the liver tissue. In group A, there were normal hepatic cords. In the group C, there was fibrosis interval formation and portal area expansion and fibrotie intervals extending to the lobule. The quantitative analysis of Mas-son staining showed that the collagen quantities in group B was higher than that of other group(P<0.01). The collagen quantities in group A was lower than that of group C(P<0.05). The results of immanohistochemical staining showed that the expression of a-SMA in group B was strong positive, middle positive in group C, and weak positive in group A (P<0.05). Conclusion The valsartan has preventive and treatment effects on hepatic fibrosis in rats of hepatic fibrosis model induced by DMN, and the preventive effect of valsartan is better than its treatment effect. The valsartan can ameliorate the hver cirrhosis by partly suppressing the activation of HSC.