Aim To study the effect of gamma-hydroxybutyric acid receptor(GHBR ) on neuronal apoptosis suffering from focal cerebral ischemia-reperfusion injury in rats. Methods The male Sprague-Dawley rats weighing 240～280 g were randomly divided into seven groups: sham operation group(sham), ischemia-reperfusion group(Isc/R) ,NCS-356 160、320、640 ?g?kg-1 group(N1、N2、N3),NCS-382 640+NCS-356 640 ?g?kg-1 group(NCS-382+N3),and nimodipine 600 ?g?kg-1 group(Nim).The middle cerebral artery occlusion(MCAO) model invented by Zea Longa with modifications was adopted. The experiment was divided into two parts after ischemia reperfusion for 24h:In the first part,we measured the cerebral expression of Bax, Bcl-2, Caspase-3 by immuneohistochemical method. In the second part,we measured neuronal apoptotic rate by flow cytometry in the ischemic cortex region. Results The expression rate of Bcl-2 and Bcl-2/Bax ratio of N1,N2,N3 and Nim groups were all higher than that of Isc/R group(P

Objective To investigate the effects of swimming exercise training on left ventricular (LV)remodeling and its possible mechanism in spontaneous hypertensive rats (SHR).Methods Twenty eightweek-old male SHRs were divided into SHR control (SC) group and SHR exercise training (ST) group,with 10 rats in each group.Ten eight-week-old male Wistar rats were used as normal control (WC) group.The ST group was subject to 60-min moderate swimming exercise without loading once daily,6 times a week,for a total of 12 weeks; while the SC and WC group had no special intervention.The blood pressure was examined once weekly.After 12 weeks,the norepinephrine (NE)and serum angiotonin Ⅱ (ANG Ⅱ) levels were determined by ELISA.The LV hypertrophy was assessed by analysing the ratio of LV weights to body weights (LVW/BW) and cardiomyocyte diameter.The collagen deposited in LV was detected by sirius red staining.The expressions of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) in LV were determined by semi-quantitative real time-polymerase chain reaction (RT-PCR) and Western blotting.Results After 12 weeks,the blood pressure,serum NE and ANG Ⅱ levels,LVW/BW ratio,cardiomyocyte diameter and collagen volume fraction (CVF) increased significantly in SC group compared with WC group; while those in ST group decreased significantly.In addition,in ST group the mRNA and protein expressions of TNF-α,IL-6,IL-1 βand TGF-β1 also decreased significantly.Conclusions The swimming exercise could reduce the blood pressure of SHR and improve LV remodeling.This effect was mediated not only by improving the hemodynamics,but also by decreasing sympathetic nerve and renin-angiotensin system (RAS) activities,decreasing the gene expressions of cytokines.The swimming exercise may be an effective strategy for improving LV remodeling in hypertension.

AIM:To study the protective effects of penehyclidine hydrochloride(PHC) on transient forebrain ischemia reperfusion injury in gerbils.METHODS:The model of transient forebrain ischemia reperfusion was established in gerbils by bilateral carotid artery clamping.The effects of PHC on neurological function scores and the morphous of hippocampal pyramidal neuron of gerbils were observed after receiving transient forebrain ischemia reperfusion.SOD activities and contents of MDA in the hippocampus and cortex of gerbils were measured.RESULTS:In the groups of PHC(0.08),(0.24)(mg?kg~(-1)) and atropine,the stroke index was decreased,compared with the ischemia-reperfusion group after the gerbils received transient forebrain ischemia reperfusion for six hours.PHC could reduce the degree of injury in hippocampal pyramidal neuron after ischemia reperfusion for three days.CONCLUSION: PHC has protective effects on transient forebrain ischemia reperfusion injury in gerbils.

This study examined the change of p16(INK4a) and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18 post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16(INK4a) and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16(INK4a) and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P<0.01). Moreover, the percentage of p16(INK4a)-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P<0.01). The percentage of p16(INK4a)-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P>0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P<0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P<0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16(INK4a) and PCNA protein (r=-0.323, P<0.05; r=0.647, P<0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16(INK4a) protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.

ObjectiveTo explore the effects of recombinant human growth hormone(rhGH)on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction (AMI). MethodsRats with AMI induced by left anterior descending coronary branch ligation were randomized to rhGH and control groups compared with sham-operated group. The effects of 4 weeks of therapy with GH starting 24 hours after myocardial infarction on myocardial cytokines expression and heart function were studied. Myocardial inflammation was examined by analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. ResultsThe levels of TNF-α, IL-1β, IL-6 and IL-10 in the infarcted and non-infarcted region of control group were markedly elevated compared to sham-operated group (all P＜0.05). After 4 weeks therapy, rhGH reduced the expression of TNF -α, IL-1β, IL-6 and increased IL-10 expression in the infarcted and non-infarcted region of rhGH group compared to control group (all P＜0. 05 ). Echocardiography showed that rhGH markedly improved left heart function (P＜0. 05 ). ConclusionsEarly rhGH treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One of immunopharmacologic mechanisms underlying the beneficial effects of rhGH on heart function improvement may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.

OBJECTIVETo evaluate the changes in the renal function of patients with chronic hepatitis B (CHB) receiving adefovir dipivoxil (ADV) or telbivudine (L-DT) monotherapy.

METHODSThis retrospective analysis involved 101 patients with CHB and liver cirrhosis receiving either ADV or L-DT monotherapy for 52 weeks. Serum creatinine, estimates of glomerular filtration rate (eGFR), and the percentage of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) at week 52 were compared with the baseline data between the two groups.

RESULTSThe mean changes of CR at week 52 from baseline were +0.05 mg/dl in ADV group and -0.12 mg/dl in L-DT group, showing a significant difference between the two groups (P=0.000). No patient was found to have an elevation of creatinine over 0.50 mg/dl. The median change of eGFR at week 52 from baseline differed significantly between ADV and L-DT groups (-4.09 vs+18.32 ml·min(-1)·1.73 m(-2), P=0.000). Ninety-two percent (12/13) of the patients with baseline eGFR<90 ml·min(-1)·1.73 m(-2) shifted to eGFR ≥90 ml·min(-1)·1.73 m(-2) after 52 weeks of L-DT treatment, as compared to 38% (3/8) in ADV group. The proportion of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) in L-DT group increased from 76.36% (42/55) at baseline to 94.55% (52/55) at week 52, while that in ADV group decreased from 82.61% (38/46) at baseline to 78.26% (36/46). The constituent ratios of eGFR at different levels were similar at baseline (P=0.443) but significantly different at week 52 between the two groups (P=0.015).

CONCLUSIONL-DT treatment is associated with a renoprotective effect in patients with CHB, but the mechanism remains unclear.

Adenine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; Hepatitis B, Chronic ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Retrospective Studies ; Thymidine ; analogs & derivatives ; therapeutic use ; Young Adult

Baculoviridae ; genetics ; Cloning, Molecular ; DNA, Recombinant ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Genetic Vectors ; Hepatitis A virus ; genetics ; immunology ; Humans ; Immunoglobulin Fab Fragments ; genetics ; Plasmids ; genetics ; Polymerase Chain Reaction ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection

This study examined the change of p 16INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16INK4a and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16INK4a and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P＜0.01). Moreover, the percentage of p16INK4a-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P＜0.01). The percentage of p16INK4a-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P＞0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P＜0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P＜0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16INK4a and PCNA protein (r=-0.323, P＜0.05; r=0.647, P＜0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16INK4a protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.

Objective:To explore the correlation between the index of hemodynamics in perinatal period and retinopathy of prematurity(ROP), so as to provide basis for the better prevention and treatment of ROP.Methods:From May 2017 to April 2019, the preterm infants were admitted to the Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University at birth and were hospitalized for more than 2 weeks, gestational age ≤ 35 weeks and birth weight ≤ 2 500 g. They were selected as the study objects.The perinatal data including heart rate, blood pressure, patent ductus arteriosus, ventricular septal defect, and NT-proBNP level on the 1 st, 7 th and 14 th day, respectively after birth were collected.They were divided into ROP group and non ROP group according to the results of the retinopathy screening report.The influencing factors of ROP were screened out by univariate analysis and multivariate regression analysis. Results:A total of 1 119 subjects were included, 105 infants with ROP were detected, and the prevalence of ROP was 9.4%.Among them, 12 cases of pre-threshold lesion type 1 and threshold lesions required treatment, accoun-ting for 1.07% of screened preterm infants .Univariate analysis and multivariate regression analysis revealed that gestational age, birth weight, total oxygen therapy time, and intrauterine growth restriction were all factors affecting ROP, and 2 hemodynamic related indicators, such as the level of NT-proBNP in plasma on the 14 th day after birth, and placenta previa or abruption were also related to ROP( OR=0.604, 0.647, 1.276, 2.361, 1.688 and 2.506, respectively, all P<0.05). Conclusion:The hemodynamic changes in perinatal period may be involved in the formation of ROP, and it is necessary to further clarify its mechanism.

BACKGROUNDHepatocyte growth factor (HGF) inhibits the development of pulmonary artery hypertension (PAH) by reducing pulmonary artery pressure and right ventricle (RV) hypertrophy. However, whether HGF can prevent RV remodeling via inhibiting apoptosis in RV cardiomyocytes and decreasing neurohormonal activation remains unknown.

METHODSThe PAH and subsequent RV remodeling in rats were induced by subcutaneous injection of monocrotaline (MCT). The PAH rats were transfected with adenovirus carrying HGF (Ad-HGF) via intratracheal instillation. Three weeks after transfection, the hemodynamics indexes were measured, serum levels for angiotonin II (ANG II) and brain natriuretic peptide (BNP) were determined by ELISA. Histological analysis was used to assess the RV hypertrophy and fibrosis. The cardiomyocyte apoptosis in RV was assayed by TUNEL staining. The mRNA expression of BNP, angiotensin-converting enzyme (ACE), Bax and Bcl-2 in RV was determined by reverse transcriptase polymerase chain reaction (RT-PCR), the protein expression of transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α in RV was determined by Western blotting.

RESULTSHGF treatment significantly decreased the mean PAH, RV systolic pressure, serum ANG II and BNP levels. HGF treatment also significantly decreased the RV hypertrophy, collagen deposition, and the number of apoptotic cardiomyocytes. Moreover, HGF treatmemt significantly decreased the expression of BNP, ACE, Bax, TGF-β1, and TNF-α, while it significantly increased the expression of Bcl-2.

CONCLUSIONSGene transfer of HGF decreases MCT-induced PAH and improves RV remodeling. This effect is mediated not only by improving the hemodynamics but also by decreasing neurohormonal activation and inhibiting cardiomyocytes apoptosis. HGF gene treatment may be an effective strategy for improving RV remodeling in MCT-induced PAH.

Animals ; Apoptosis ; genetics ; physiology ; Hepatocyte Growth Factor ; genetics ; physiology ; therapeutic use ; Humans ; Hypertension, Pulmonary ; metabolism ; therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; genetics ; physiology