OBJECTIVES: To investigate the molecular mechanism by which salvianolic acid B (Sal-B) modulates mitochondrial functional homeostasis and alleviates myocardial ischemia-reperfusion (I/R) injury in mice. METHODS: Mouse cardiomyocyte HL-1 cells were pretreated with 5 μmol/L Sal-B with or without sh-Sirt1 transfection before exposure to hypoxia-reoxygenation (HR), and the changes in ATP production, mitochondrial superoxide activity, substrate oxidation level were evaluated. In the animal experiment, 36 C57BL/6J mice were randomized into 3 groups (n=12) for sham operation or ligation of the left anterior coronary artery to induce myocardial I/R injury with or without intravenous injection of Sal-B+I/R (50 mg/kg). In the rescue experiment, 60 adult C57BL/6J mice were randomized into 5 groups (n=12): sham-operated group, myocardial I/R group, Sal-B+I/R group, I/R+Sal-B+Sirt1fl/fl group, and I/R+Sal-B+cKO-Sirt1 group. Myocardial injury was evaluated with HE staining, and cardiac function was assessed by measurement of the ejection fraction and fractional shortening using echocardiography. RESULTS: In HL-1 cells with HR injury, Sal-B pretreatment significantly increased cellular ATP production, reduced mitochondrial superoxide anion levels, and enhanced oxygen consumption level. In the mouse models of myocardial I/R injury, Sal-B pretreatment markedly ameliorated I/R-induced structural disarray of the cardiac myocytes and improved cardiac ejection. Cycloheximide chase with Western blotting and ubiquitination assays after Sirt1-IP showed that Sal-B significantly inhibited Sirt1 degradation in HL-1 cells. Sirt1 knock-down reversed Sal-B-induced increases in ATP production, reduction in superoxide, and elevation of OCR in HL-1 cells. Cardiomyocyte-specific Sirt1 knockout obviously reversed Sal-B-mediated improvement in cardiac ejection function and myocardial structure damage in mice with myocardial I/R injury. CONCLUSIONS Sal-B promotes mitochondrial functional homeostasis in cardiomyocytes with HR injury and improves cardiac function in mice after myocardial I/R by inhibiting Sirt1 protein degradation.
Animals ; Sirtuin 1/metabolism* ; Myocardial Reperfusion Injury/physiopathology* ; Mice, Inbred C57BL ; Mice ; Myocytes, Cardiac/drug effects* ; Benzofurans/pharmacology* ; Homeostasis/drug effects* ; Male ; Mitochondria/drug effects* ; Depsides

Objective To investigate the feasibility and safety of colorectal anastomosis using nickel titanium compression anastomosis ring (CAR).MethodsThe clinical data of 83 patients who received colorectal anastomosis at the First Affiliated Hospital of Fujian Medical University from May to December,2010 were prospectively analyzed.All patients were divided into CAR group (41 patients) and stapler group (42 patients) according to the random number table.The operation time,time to postoperative flatus and bowel movement,duration of hospital stay and the incidence of anastomosis-related complications of the 2 groups were observed.The time of extrusion of the rings and anastomotic healing of the CAR group were recorded.All data were analyzed by the t test or chi-square test.ResultsThe mean operation time of the CAR group and the stapler group were ( 122 ± 25) minutes and (128 ±30)minutes,respectively.The incidences of postoperative anastomotic fistula of the CAR group and the stapler group were 5％ (2/41) and 7％ (3/42),and the anastomotic fistula was cured by operation or conservative treatment.There were no significant differences in the mean operation time,time to postoperative flatus and bowel movement,duration of hospital stay and incidence of anastomotic fistula between the 2 groups (t =1.299,0.756,1.636,0.974,x2 =0.165,P ＞ 0.05 ).The rings were expelled within 9-14 days.The incidences of anastomotic stenosis of the CAR group and stapler group were 0 (0/41) and 2％ (1/42),with no significant difference between the 2 groups (x2 =0.988,P ＞ 0.05).The anastomotic stoma was smooth and well bealed in the CAR group,while nail residues and inflammatory polyp (1 patient) were found at the anastomosis stoma in the stapler group.ConclusionNickel titanium CAR is safe and effective in colorectal anastomosis.