Objectiv

e      To determine the role of gastrin in the protection of myocardial ischemic/reperfusion (I/R) injury in isolated Sprague-Dawley (SD) rat hearts and the role of STAT3 in the process.       Methods      Forty-eight healthy adult male SD rats of SPF grade

weighing 250 to 300 g were randomly divided into 4 groups (n=12 for each group

6 SD rats were subjected to measure left ventricular function

infarct size and myocardial enzymes

and the others were used to perform TUNEL assay and Western blotting)

that is

blank group

gastrin pretreatment group (gastrin group)

I/R injury group (IR group)

and gastrin pretreatment and I/R injury group (GIR group). Isolated rat hearts were perfused with a Langendorff device. Blank group were infused with Krebs-Henseleit (K-H) buffer continuously for 130 min. For gastrin group

gastrin (10

-9

mol/L) was added in 10 to 30 min after the K-H buffer perfusion. For IR group and GIR group

the K-H buffer perfusion was stopped after 30 minutes’ perfusion

and then the hearts experienced 40 minutes’ non-perfusion and 60 minutes’ reperfusion. For GIR group specially

gastrin (10

-9

mol/L) was infused for 20 min after 10 minutes’ K-H buffer perfusion. Left ventricular end diastolic pressure (LVEDP)

left ventricular developed pressure (LVDP) and maximal rate of rise of left ventricular pressure (+dp/dt

max

) were measured at time points immediately before the perfusion blocking (T0)

15 min-reperfusion (T1)

30 min-reperfusion (T2)

45 min-reperfusion (T3) and 60 min-reperfusion (T4). The eluate of coronary sinus was collected at T0 and T4 respectively to measure the contents of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB). After the experiment

the hearts were subjected to TTC staining for infarct size. TUNEL assay was used to detect cell apoptosis for the myocardiocytes

and Western blotting for STAT3 and phosphp-STAT3 assessment.       Results      There were no differences in all the following indexes between the blank and gastrin

groups (P0.05). In IR group and GIR group

LVEDP was increased

while LVDP and +dp/dt

max

were decreased at the time points from T1 to T4

the infarct size was exaggerated

the contents of LDH and CK-MB were elevated

cell apoptosis was enhanced and the expression of p-STAT3 was increased when compared with blank and gastrin groups (P0.05). Gastrin pretreatment resulted in improved LVEDP

LVDP and +dp/dt

max

from T1 to T4 time points (P0.05)

reduced infarct size (P0.05)

lower contents of LDH and CK-MB (P0.05)

ameliorated cell apoptosis [(19.2±1.0)% vs (14.2±1.0)%

P0.05

]

and enhanced STAT3 phosphorylation compared with IR group (1.14±0.10 vs 1.63±0.10

P0.05).       Conclusion       Gastrin protects the myocardial injury against ischemia and reperfusion through STAT3 pathway.