ABSTRACT
Objective To evaluate the effect of capsaicin on cardiac dysfunction in diabetic rats u-sing an in vitro experiment. Methods Healthy male Sprague-Dawley rats, weighing 240-260 g, in which type 1 diabetes mellitus was induced by intraperitoneal streptozotocin 50 mg∕kg, were studied. Eighteen di-abetic rats were selected at 8 weeks after successful establishment of the model and divided into 3 groups (n=6 each)using a random number table: diabetes mellitus group(DM group), capsaicin group(CAP group)and capsaicin plus capsazepine group(CPZ group). Another 8 rats with normal blood glucose served as control group(C group). Rat hearts were quickly removed under deep anesthesia and retrogradely perfused with an oxygen-saturated K-H solution(at 37℃)using a Langendorff apparatus. Cardiac function was maintained stable for 10 min. The hearts were continuously perfused with K-H solution for 30 min in C and DM groups. The hearts were perfused with K-H solution for 20 min, and capsaicin(1.4×10-9g∕L)was then infused for 10 min via the branch of aortic cannula using micro pump in CAP group. The hearts were perfused with K-H solution for 10 min, and capsaicin receptor-transient receptor potential vanilloid type 1 antagonist capsazepine(1.4×10-7g∕L)was then infused for 10 min followed by infusion of capsaicin(1.4× 10-9g∕L)at 0.5 ml∕min for 10 min via the branch of aortic cannula using a micro-pump in CPZ group. Left ventricular systolic pressure(LVSP), left ventricular developed pressure(LVDP), left ventricular end-di-astolic pressure(LVEDP), heart rate, the maximum rate of increase or decrease in left ventricular pres-sure(±dp∕dtmax)were recorded at 10, 20 and 30 min of continuous infusion(T1-3). Results There was no significant difference in LVEDP and ± dp∕dtmaxat each time point among the four groups(P>0.05). Compared with C group, LVSP and LVDP were significantly decreased at T1-3in DM and CPZ groups and at T1-2in CAP group, and heart rate was significantly decreased at T1-3in DM, CPZ and CAP groups(P<0.05). Compared with DM group, LVSP and LVDP were significantly increased at T3in CAP group(P<0.05), and no significant change was found in LVSP or LVDP in CPZ group(P>0.05). LVSP and LVDP were significantly lower at T3in CPZ group than in CAP group(P<0.05). Conclusion Capsaicin can mitigate cardiac dysfunction in diabetic rats, and the mechanism is related to activating transient receptor potential vanilloid type 1.
ABSTRACT
Objective The aim of the study was to investigate the diabetic neuro-degeneration and its changes in neuroreaction to myocardial ischemia and reperfusion,by evaluation of the altera-tion of noxious thermal threshold and expression of substance P (SP),calcitonin gene related peptide (CGRP)in dorsal root ganglia in upper thoracic segments (T1-5 )in diabetic rats.Methods Thirty two male Sprague-Dawley rats,weighing 180-200g,were randomly divided into control group (group C)and diabetic group (group DM),1 6 rats in each group.rats in DM group were fed with high sug-ar-fat diet for 14 weeks and were given streptozotocin (STZ,35 mg/mg,i.p.)at the end of the 4 th week,to set up diabetes experimental model.The animals in control group were fed with standard la-boratory diet.Tail flick latency to thermal stimulation was measured weekly.At the end of 10 weeks after administration of STZ,diabetic rats (and rats in control group)were further divided into myo-cardial ischemia-reperfusion group (group IR)and sham operation group (group Sham).The left an-terior descending branch of coronary artery was occluded for 30 min followed by reperfusion for 120 min,establishing myocardial ischemia-reperfusion.The histological immunofluorescence assay and Enzyme-linked immunosorbent assay (ELISA)were carried out to evaluate the changes of the expres-sions of CGRP and SP in the dorsal root ganglia.Results The tail flick latency was significantly in-creased in group DM,compared to the group C (P < 0.01).The immunoreactive materials for CGRP and SP in the sensory neurons in dorsal root ganglia of upper thoracic segments (T1-5 )were markedly declined in group DM (P <0.01 or P < 0.05).Furthermore,levels of SP and CGRP were signifi-cantly lower in the DRG of the group IR after myocardial ischemia-reperfusion,compared to that in the group sham (P <0.01).Conclusion Diabetes causes sensory denervation and obvious reduction of expression of SP and CGRP in the sensory neuron innervating heart during myocardial ischemia-reper-fusion,indicating impairment of adaptive reactivity of neuro-endocrine function of cardiac sensory nerves.