Sophocarpine ameliorates cardiac hypertrophy through activation of autophagic responses.

Mounting evidences indicate that autophagy is an essential homeostatic mechanism to maintain the global cardiac structure function. Sophocarpine (SOP), a major bioactive compound derived from the natural plant Sophora flavescens. However, the role of SOP in cardiac hypertrophy remain to be fully elucidated. In the present study, we tested the hypothesis that SOP protects against Ang II-induced cardiac hypertrophy by mediating the regulation of autophagy. The results demonstrated that SOP attenuated the Ang II-induced cardiac hypertrophy, as assessed by measurements of echocardiography parameters, the ratios of heart weight/body weight and left ventricle weight/body weight, histopathological staining, cross-sectional cardiomyocyte area, and the expression levels of cardiac hypertrophic markers. The anti-hypertrophic effect of SOP was mediated by activating autophagy-related pathway, as revealed by reversal of the increased autophagy marker protein expression. These findings reveal a novel mechanism of SOP attenuating cardiac hypertrophy via activating autophagy-related signaling pathways.

Puerarin Alleviates Lipopolysaccharide-Induced Myocardial Fibrosis by Inhibiting PARP-1 to Prevent HMGB1-Mediated TLR4-NF-κB Signaling Pathway.

Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 and HMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin on MFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway in LPS-induced primary CFs and TAC-induced MFs rats' model.

[Analysis of the cause and clinical characteristics of maternal cardiac arrest].

OBJECTIVE: To analyze the cause and clinical characteristics of maternal cardiac arrest. METHODS: The data of all cases of maternal cardiac arrest from January 2005 to December 2009 in Third Affiliated Hospital of Guangzhou Medical College was retrospectively studied. RESULTS: (1) A total of 41 maternal cardiac arrests (6 in prenatal period, 2 in the first stage of labor, 7 in the third stage of labor, 26 in postpartum period) were included. All patients regained spontaneous circulation after basic life support. Twelve (29%) mothers survived. Twelve cardiac arrests occurred in the hospital, and the total delivery number from January 2005 to December 2009 was 17 101, with occurrence rate of 1:1425. (2) The causes of arrest were hemorrhagic shock (12, 29%), amniotic fluid embolism (7, 17%), severe preeclampsia/eclampsia (7, 17%), septic shock (6, 15%), cardiac disease (2, 5%), unidentified cause (2, 5%) and other occasional causes. (3) Thirty-seven (90%) in-hospital maternal cardiac arrest occurred in operation room (16, 39%), ICU (7, 17%), maternity wards (6, 15%), delivery room (5, 12%) and the emergency room (3, 7%). Three (7%) arrest occurred out of hospital and one in the ambulance. Maternal survival rate was 2/3 in the emergency room, 8/16 in the operation room, 1/5 in the maternity wards, and 1/6 in the delivery room. No mother survived in ICU, ambulance or out of hospital. (4) Five of the 12 survived women showed ischemic encephalopathy after cardiac arrest and one of them developed cerebral infarction in the right corona radiate. (5) In 4 of the 8 cases of cardiac arrest in pregnancy, perimortem caesarean section (PMCS) was performed. In the four PMCS, 2 mothers and 2 children survived. In the 4 cases that PMCS was not carried out, no infant survived. CONCLUSIONS: Hemorrhagic shock, severe preeclampsia and eclampsia, amniotic fluid embolism are the major obstetric causes of maternal cardiac arrest. Septic shock and cardiac diseases are the major non-obstetric causes. Cardiac arrests occurred in emergency room and operation room has a higher maternal survival rate than those occurred in the delivery room and maternity wards. Timely PMCS may ensure the optimal outcome for mothers and fetuses.

[Clinical outcomes and characteristics of concurrent eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome].

OBJECTIVE: the purpose was to describe the outcomes and characteristics of the obstetric patients with concurrent eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) syndrome. METHODS: we retrospectively collected the materials between December 1999 and December 2008 in Obstetric Critical Care Center of Guangzhou. There were 76 patients in rolled then they were divided into two groups according to with or without HELLP syndrome. All the patients were injected Magnesium Sulfate to control seizure and to prevent the recurring of seizure. We analyzed the characteristics (such as age, gestational weeks, blood pressure after seizure), complications, biochemistry markers, the rate for intensive care unit (ICU) admittion, the need for mechanical ventilation, the Glasgow coma score (GCS) when admitted into ICU, computed tomography scan (CT) or magnetic resonance imaging (MRI), death rate of maternal and others, then compared between the two groups. RESULTS: (1) general data: There were 17 patients admitted with both eclampsia and HELLP syndrome, and 59 patients admitted eclampsia without HELLP syndrome. The incidence of eclampsia with HELLP syndrome was 22% (17/76). In eclampsia with HELLP syndrome group, the systolic blood pressure was higher and the rate of preterm also was higher [(182 ± 20) mm Hg (1 mm Hg = 0.133 kPa) vs. (159 ± 21) mm Hg, P < 0.05]. But in regard to the age, gestational weeks, the rate of regular prenatal care and diastolic blood pressure, there were no differences between the two groups. (2) Biochemistry markers: the aspartate transaminase (AST), lanine transaminase (ALT), blood urea nitrogen and creatinine were significantly increased in eclampsia with HELLP syndrome group than eclampsia without HELLP syndrome group [(879 ± 337) U/L vs. (90 ± 27) U/L, (344 ± 83) U/L vs. (43 ± 11)U/L, (2245 ± 294) U/L vs. (485 ± 61) U/L, (14 ± 9) mmol/L vs. (7 ± 3) mmol/L, (140 ± 92) µmol/L vs. (83 ± 28) µmol/L, P < 0.01, P < 0.05], and the platelet was lower in eclampsia with HELLP syndrome group [(38 ± 13) × 10(9)/L vs (172 ± 46) × 10(9)/L, P < 0.01]. (3) Clinical outcomes: The maternal death rate was 35% (6/17) in eclampsia with HELLP syndrome patients, and significantly higher than the rate in eclampsia without HELLP syndrome group (3%, 2/59) (P < 0.05). There were more patients admitted to ICU and more patients who need mechanical ventilation in eclampsia with HELLP syndrome (13/17 vs. 34%, 9/17 vs. 24/, P < 0.05), also more patients with GCS ≤ 8 in eclampsia with HELLP syndrome when admitted to ICU (8/17 vs. 7/59, P < 0.05), compared to the eclampsia without HELLP syndrome group. There were more patients complicated with cerebral venous thrombosis and cerebral hemorrhage in eclampsia with HELLP syndrome group than other group (8/17 vs. 7%, P < 0.05). Five of six patients died of cerebral hemorrhage in eclampsia with HELLP syndrome group, while other two missing cases in eclampsia without HELLP syndrome group all died of cerebral hemorrhage. The all missing cases were performed CT or MRI and seven (7/8) of them showed cerebral hemorrhage. CONCLUSION: the incidence of concurrent eclampsia and HELLP syndrome was not rare, it happened seriously and with more mortalities, such as cerebral hemorrhage, and also the maternal mortality rate was significantly higher. It should be warning that the obstetrician should take great attention for these women, and consider life support treatment for them.

[Establishment of a neonatal piglet model of multiple organ dysfunction syndrome].

OBJECTIVE: To study the reliability of establishing a neonatal piglet model of multiple organ dysfunction syndrome (MODS) by cecal ligation and puncture (CLP). METHODS: Fourteen neonatal piglets were randomly assigned into Experiment group (n=9) and Control group (n=5). MODS model was established in the piglets from the Experiment group by CLP. The Control group underwent a sham-operation. Serum biochemical parameters (ALT, AST, ALB, BUN, Cr, CK-MB and lactic acid), blood platelet counting and blood gas analysis(PaO2 and PaCO2) were tested at 0, 24, 48, 72, 96, and 120 hrs after operation. The histomorphological changes of important vital organs were examined by hematoxylin-eosin staining under a light microscope. RESULTS: The levels of serum ALT, AST, BUN, Cr, CK-MB and lactic acid in the Experiment group began to increase 24 hrs after operation. Significant differences were observed between the Experiment and the Control group at 48 hrs in ALT (83.0 +/- 9.3 U/L vs 57.8 +/- 15.8 U/L), AST (348.8 +/- 132.9 U/L vs 106.4 +/- 12.5 U/L), BUN (10.5 +/- 2.5 micromol/L vs 4.3 +/- 1.0 micromol/L), Cr (79.2 +/- 9.0 micromol/L vs 53.6 +/- 6.8 micromol/L), CK-MB (5152.0 +/- 1 857.8 U/L vs 1243.0 +/- 354.5 U/L), and lactic acid (12.3 +/- 4.0 mmol/L vs 4.6 +/- 1.5 mmol/L) (P < 0.01). The high levels of the above parameters persisted until 96 hrs after operation in the Experiment group and then decreased but were still higher than those at 0 h after operation. After operation, the blood platelet counting decreased significantly at 96 hrs, and PaO2 decrease and PaCO2 increase were observed at 48 hrs in the Experiment group compared with the Control group. All animals, except one, in the Experiment group died within 120 hrs after operation (with the MODS incidence of 56%), while none died in the Control group. The tissue injuries with different degrees were observed in the lungs, liver, heart, kidneys and gastrointestinal tracts of the Experiment group. CONCLUSIONS: Neonatal piglet MODS model can be established successfully by CLP.