AIM:To observe the time pattern of intrinsic myocardial dysfunction and other organ dysfunction in a rat model of mild cecal ligation and puncture (CLP).METHODS:Male SD rats were randomly divided into sham group and CLP group.At 6 h, 9 h and 12 h after sham operation or CLP, intrinsic myocardial systolic and diastolic functions were determined by Langendorff system.The expression of cardiac tumor necrosis factor (TNF)-α, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was measured.In addition, serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as blood urea nitrogen (BUN) were analyzed.For evaluating pulmonary edema, the lung wet-dry weight (W/D) ratio was calculated.RESULTS:In mild CLP rats, the mortality rate was 26.7% on day 10 after CLP.At 9 h and 12 h after CLP, the maximum rate of positive and negative changes in left ventricular pressure (±dp/dt) were decreased in CLP group compared with sham group.At 6 h after CLP, cardiac mRNA expression of TNF-α, ICAM-1 and VCAM-1 was increased in septic rats compared with the controls.At 9 h after CLP, cardiac protein levels of TNF-α and VCAM-1 were higher in CLP group than that in sham group (P<0.05).The serum AST activity at 9 h and ALT activity at 12 h after CLP were increased in CLP group compared with sham group.However, no difference in BUN and lung W/D ratio at 6 h, 9 h and 12 h between CLP group and sham group was observed.CONCLUSION:Our findings highlight the presence of intrinsic myocardial dysfunction at 9 h after CLP in a rat model of mild CLP.Intrinsic myocardial dysfunction occurs earlier than the liver and kidney dysfunctions.

AIM: To observe the effects of berberine (Ber) on enterocyte apoptosis in septic mice and its pos-sible mechanism.METHODS: Male C57BL/6 mice (8 ~10 weeks old) were randomly divided into sham group, cecal ligation and puncture (CLP) group, CLP +Ber group and sham +Ber group.The mice in CLP group underwent CLP ope-ration, and the mice in sham groups suffered a similar operation except the ligation and puncture.After the sham or CLP operation, the mice were administered intragastrically with distilled water or berberine (50 mg/kg) within 2 h.After 20 h, the mice were killed with excess pentobarbital sodium and the ileum tissues were removed.The histological changes of the intestine were observed and the enterocyte apoptosis was examined by determining the protein level of cleaved caspase-3. Furthermore, mitochondrial Bax, cytoplasm cytochrome C (Cyt C) and the total proteins of Bcl-2, Fas, FasL and Fas-as-sociated protein with death domain (FADD) were examined by Western blot.The mRNA expression of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was measured by real-time PCR.RESULTS: The extensive ileum injuries, including remarkably increased leukocytes and necrosis of intestinal villus were observed 20 h after CLP.In CLP group, the protein levels of cleaved caspase-3, cytoplasm Cyt C, as well as Fas, FasL were significantly increased, but the Bcl-2 level was decreased.Bax translocation into mitochondria was promoted.However, FADD was not changed significantly.The mRNA expression of TH and DBH was also increased sharply in CLP group.On the contrary, treatment with berberine made a considerable alleviating alteration in the ileum of the septic mice.CONCLUSION: Treatment with berberine pro-vides protective effects on intestinal injury in septic mice by reducing enterocyte apoptosis, and its possible mechanism may be involved in the inhibition of the endogenous and exogenous apoptosis pathways.

AIM:To observe the effect of B-HT933, a selective α2-adrenoceptor agonist, on lipopolysaccha-ride ( LPS )-induced TNF-αproduction in neonatal rat cardiomyocytes and to explore the underlying mechanisms . METHODS:The neonatal rat cardiomyocytes were cultured .The localization of α2A-adrenoceptor in the cardiomyocytes was examined by immunofluorescence staining .The cardiomyocytes were exposed to LPS or/and B-HT933 for different time.The level of TNF-αin the supernatants and the mRNA expression of TNF-αwere detected by ELISA and real-time PCR, respectively.In addition, LPS-associated signal molecules in the cardiomyocytes were also examined by Western blotting.RESULTS: Immunofluorescence staining showed that α2A-adrenoceptors were localized in the cardiomyocytes . LPS stimulated TNF-αproduction in the cardiomyocytes in a dose and time-dependent manner .B-HT933 pretreatment sig-nificantly inhibited the expression of TNF-αat mRNA and protein levels in LPS-treated cardiomyocytes .Furthermore, LPS exposure induced IκBαand p38 phosphorylation in cardiomyocytes and only IκBαphosphorylation was prevented by B-HT933 treatment.CONCLUSION:α2A-adrenoceptors are present in neonatal rat cardiomyocytes and its agonist B -HT933 inhibits LPS-induced TNF-αproduction in cardiomyocytes via suppressing IκBαphosphorylation .