ABSTRACT
Objective To evaluate the effect of hydrogen sulfide on myocardial exogenous apoptotic pathway in a rat model of hemorrhagic shock and resuscitation.Methods Sixty clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n =15 each) using a random number table method:sham operation group (group S),sham operation plus sodium sulphid (NaHS) group (group S+NaHS),hemorrhagic shock group (HS group),and hemorrhagic shock plus sodium sulphid group (group HS+NaHS).Rats only underwent arterial and intravenous puncture in group S.Hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 35-40 mmHg within 10 min and maintained for 1.5 h.NaHS 28 μmol/kg was intraperitoneally injected at 10 min before resuscitation in group HS+NaHS.The equal volume of NaHS was administered at the same time in group S+NaHS.Immediately before blood letting and at 0,1.5,2,3,4 and 6 h after blood letting (T1-5),MAP was recorded and blood samples were collected from the femoral vein for determination of serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations by chemical colorimetry.Rats were then sacrificed and hearts were removed for examination of the pathological changes of myocardial tissues (with a light microscope) and for determination of cell apoptosis (by TUNEL),expression of caspase-3 and caspase-8 (by Western blot) and expression of Fas and FasL (by immunohistochemistry).Apoptosis index was calculated.Results Compared with group S,MAP was significantly decreased at T1-5,the serum CK and LDH concentrations at T1-5 and apoptosis index at T5 were increased,and the expression of Fas,FasL,caspase-3 and caspase-8 was up-regulated in group HS (P＜ 0.05).Compared with group HS,MAP was significantly increased at T1-3,the serum CK and LDH concentrations at T3-5 and apoptosis index at T5 were decreased,and the expression of Fas,FasL,caspase-3 and caspase-8 was down-regulated in group HS+NaHS (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group HS+NaHS when compared with group HS.Concclusion The mechanism by which hydrogen sulfide attenuates myocardial injury induced by hemorrhagic shock and resuscitation is associated with inhibiting the exogenous apoptotic pathway in rats.
ABSTRACT
Objective To evaluate the effect of curcumin on the expression of MMP-2 and MMP-9 in the spinal dorsal horn and dorsal root ganglion (DRG) of rats with type 2 diabetic neuropathic pain (DNP).Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 35 mg/kg,and confirmed by fasting blood glucose level ≥ 16.7 mmol/L in male Sprague-Dawley rats.Type 2 DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdraw latency (TWL) measured on day 14 after streptozotocin administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups (n =27 each):type 2 DNP group (group DNP); curcumin group (group Cur); solvent control group (group SC).In Cur and SC groups,curcumin 100 mg/kg and corn oil 4 ml/kg were injected intraperitonally,respectively,once a day for 14 consecutive days starting from day 14 after streptozotocin administration.Another 27 normal Sprague-Dawley male rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before type 2 DNP was induced,after type 2 DNP was induced,and at 3,7 and 14 days after curcumin injection(T1-5).The rats were sacrificed after MWT and TWL were measured at T3-5,and the lumbar segments of the spinal cord and DRG (L4-6) were removed for determination of the expression of MMP-2 and MMP-9 by Western blot.Results Compared with group C,MWT was significantly decreased and TWL was shortened,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was up-regulated in DNP,Cur and SC groups.Compared with DNP group,MWT was significantly increased and TWL was prolonged,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was down-regulated in Cur group,and no significant changes were found in the parameters mentioned above in SC group.Conclusion The mechanism by which curcumin attenuates type 2 DNP may be related to up-regulation of the expression of MMP-2 and MMP-9 in the spinal dorsal horns and DRG of rats.