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Abstrac:Aim To study the effect of hydroxysafflor yellow A ( HYSA ) on the proliferation of vascular smooth muscle cells ( VSMCs) and the related molecu-lar mechanism. Methods The inhibitory effects of hydroxysafflor yellow A on VSMC proliferation was de-tected using cell culture, MTT assay, Western blot and immunohistochemical staining. Results The results showed that HYSA inhibited cell proliferation induced by PDGF in a dose-dependent (5,10,20,40 μmol· L-1 ) manner, reduced proliferating cell nuclear anti-gen ( PCNA ) expression and blocked PDGFR-MEK-ERK1/2 signaling pathway activated by PDGF in VSMCs. Conclusion HYSA inhibits VSMCs prolifer-ation via reducing the expression of PCNA and blocking signal transduction of MEK-ERK1/2 in VSMCs.
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Objective To evaluate the effects of levosimendan on hemodynamics and cardiac function in patients with septic shock. Methods A prospective single-center randomized controlled trial was conducted. The patients with septic shock admitted to the Department of Critical Care Medicine of the Third Hospital of Hebei Medical University from June 2011 to October 2013 were enrolled. The patients with septic shock received the conventional treatment according to international guidelines for management of severe sepsis and septic shock. Thirty-six patients received the examination of echocardiography and left ventricular ejection fraction (LVEF)≤0.45 after fluid resuscitation were enrolled the study ,who were divided into two groups according to random number table ,with 18 cases in each group. After the conventional treatment,the patients in dobutamine group received intravenous injection of 5μg·kg-1·min-1 dobutamine for 48 hours immediately after fluid resuscitation,and those in levosimendan group received a 24-hour infusion of 5μg·kg-1·min-1 dobutamine followed by a 24-hour infusion of 0.2μg·kg-1·min-1 levosimendan. The hemodynamics and cardiac function were evaluated by pulse indicator continuous cardiac output (PiCCO) and ultrasound during treatment. Results Compared with dobutamine group,after the treatment in the levosimendan group,stroke volume index (SVI),cardiac index (CI)and left ventricular stroke work index(LVSWI) were significantly increased〔SVI(mL/m2):39.8±5.4 vs. 37.5±4.5,t=-2.762,P=0.020;CI(L·min-1·m-2):4.6± 0.7 vs. 3.6±0.7,t=-9.829,P=0.000;LVSWI (kg·min-1·m-2):33.7±2.4 vs. 28.2±1.2,t=-6.307,P=0.000〕, and central venous pressure (CVP),intrathoracic blood volume index (ITBVI)and extravascular lung water index (EVLWI)were significantly decreased〔CVP(mmHg,1 mmHg=0.133 kPa):8.2±0.9 vs. 12.1±0.8,t=3.928,P=0.002;ITBVI (mL/m2):820±42 vs. 978±69,t=9.472,P=0.000;EVLWI (mL/kg):6.1±1.6 vs. 8.9±1.7,t=4.467,P=0.001〕. Cardiac ultrasound showed that compared with dobutamine group,in the levosimendan group,left ventricular end-systolic volume (LVESI) and end-diastolic volume (LVEDI) were significantly lowered〔LVESI (mL/m2):32.7±9.2 vs. 48.2±13.4,t=0.882,P=0.000;LVEDI (mL/m2):61.7±11.4 vs. 78.6±13.6,t=2.453, P=0.032〕,and the LVEF was significantly increased (0.463 ±0.068 vs. 0.383 ±0.085,t=-2.439,P=0.035). Levosimendan also could decrease the lactic acid(mmol/L:3.4±1.1 vs. 5.2±1.2,t=3.346,P=0.007),and increase the lactate clearance rate(mL/min:73.2±13.5 vs. 47.6±11.8,t=-4.079,P=0.002),24-hour urinary output(mL:2 213.4±354.0 vs. 1 533.8±402.0,t=6.342,P=0.000)and 24-hour cumulative intake (mL:5 746.6±420.0 vs. 4 156.7 ±215.0,t=7.126,P=0.000). There were no significant differences in total volume of norepinephrine, mortality in intensive care unit (ICU)and 28-day mortality between two groups. Conclusion Levosimendan can increase cardiac ejection function,reduce the heart blood and vascular preload,intrathoracic lung water,improve heart function and systemic hemodynamic indexes of patients with septic shock.
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Objective To evaluate the effect of methylene blue pertreatment on acute kidney injury induced by sepsis in rats.Methods Ninety male Sprague-Dawley rats,aged 1.5-2.5 months,weighing 200-250 g,were randomly assigned into 3 groups (n =30 each) using a random number table:sham operation group (S group),cecal ligation and puncture (CLP) group and methylene blue group (MB group).The rats were anesthetized with 10％ chloral hydrate 350 mg/kg.Normal saline 0.8 ml was injected via the caudal vein in and CLP groups,while 10％ methylene blue 15 mg/kg (in normal saline 0.8 ml) was injected via the caudal vein in group MB.Sepsis was induced by CLP after the end of administration in CLP and MB groups.Twenty animals in each group were chosen and observed for 72 h survival rate.Ten animals were sacrificed in each group at 18 h after operation and kidney specimens were removed for microscopic examination and for determination of the expression of poly (ADP-ribose) polymerase (PARP-1) using immunohistochemistry and Western blot.Blood samples were taken from the heart for determination of serum concentrations of blood urea nitrogen (BUN),creatinine (Cr),cystatin C and neutrophil gelatinase-associated lipocalin (NGAL).Results Compared with group S,the survival rate was significantly decreased at 24,48 and 72 h after operation,and the serum concentrations of BUN,Cr,cystatin C and NGAL and expression of PARP-1 in kidney tissues were increased in CLP and MB groups (P ＜ 0.05).Compared with group CLP,the survival rate was significantly increased at 24 and 48 h after operation,and the serum concentrations of BUN,Cr,cystatin C and NGAL and expression of PARP-1 in kidney tissues were decreased in group MB (P ＜ 0.05).The pathological changes were significantly attenuated in group MB as compared with group CLP.Conclusion Methylene blue pertreatment can attenuate acute kidney injury induced by sepsis in rats through down-regulating the expression of PARP-1.
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Objective To compare extravascular lung water index (EVLWI) and oxygenation index (PaO2/FiO2) in estimation of acute lung injury(ALI) .Methods Sixteen patients with post traumatic ALI (within 48 h) of both sexes, aged 18-80 yr, were studied. The patients were mechanically ventilated. Right internal jugular vein and femoral artery were catheterized and connected to PiCCO monitor (IntelliVue MP50, Philips, Netherlands).EVLWI was monitored with the PiCCO system. PaO2 was determined every 24 h. ALI was diagnosed based on the following criteria:(1)PaO2/FiO2≤300 mm Hg; (2)X-ray chest film-patchy shadows in the bilateral lungs and (3) CVP≤12 mm Hg.Lung injury score(LIS) was recorded. The patients were divided into PaO2/FiO2≤ 300 group and ≤200 group and EVLWI ≥ 10 group and ＜ 10 group. Results There was no significant difference in LIS between PaO2/FiO2 ≤300 group and PaO2/FiO2 ≤200 group at 24 and 48 h of PiCCO monitoring. At 72 h of PiCCO monitoring LIS was significantly increased in PaO2/FiO2 ≤200 group as compared with PaO2/FiO2 ≤300 group, LIS was significantly higher in EVLWI≥ 10 group than in EVLWI ＜ 10 group at 24, 48 and 72 h of PiCCO monitoring. Conclusion EVLWI is more accurate than PaO2 /FiO2 in estimation of severity of ALI.