Effect Of Tongxinluo On Connexin43Remodeling In Cardiac Hypertrophy

Part1Effect of Tongxinluo on H9c2cardiomyocytes hypertrophy and expressionof Connexin43mRNA induced by isoproterenolObjective To investigate the effects of Tongxinluo (TXL) on hypertrophy of H9c2cardiomyocytes and Connexin43mRNA expression induced by Isoproterenol (Iso).Method Cultured H9c2cardiomyocytes were randomly divided into four groups:control group, TXL group, Iso group and Iso+TXL group. After72hours cultured,Cell size was determined by phase contrast microscope, the protein concentrationswere measured by BCA method and the expression of Cx43mRNA were measured byreverse transcription polymerase chain reaction (RT-PCR).Results Cell size of H9c2cardiomyocytes of the Iso group (P<0.05) was increasedmore prominently than the control group. Compared with Iso group, Tongxinluoattenuated the increase of cardiomyocytes size (P<0.05). H9c2cardiomyocytesprotein concentrations in the Iso group (P<0.05) was increased more significantlythan the control group. Although Tongxinluo didn’t affect the normal H9c2cardiomyocytes protein concentration, it inhibited the increase of proteinconcentrations induced by Iso (P<0.05).Iso decreased Cx43mRNA expression ofH9c2cardiomyocytes more evidently than that of the control group (P<0.05), whichwas inhibited by Tongxinluo (P<0.05).Conclusions Tongxinluo can prevent the hypertrophy of H9c2cardiomyocytes anddown-regulate of Cx43mRNA expression induced by Iso.Part2Effect of Tongxinluo on QT Dispersion and Connexin43Remodeling inCardiac HypertrophyObjective To explore the effects of Tongxinluo on QT dispersion and connexin43remodeling in cardiac hypertrophy induced by pressure overload. Methods Forty-five male SD rats were divided into three groups randomly:sham-operation (SO) group, abdominal aorta constriction (AC) group, abdominal aortaconstriction+Tongxinluo (AT) group. The cardiac hypertrophy model was made withabdominal aortic constriction operation. The animals in the AT group were lavagedwith Tongxinluo (1.5g/kg/d) and the animals in other groups were given with0.9%saline every day for12weeks. To measure the thickness of left ventricular wall withechocardiography, Ventricular electrophysiologies were measured by Cardiacelectrophysiological recorder, left ventricular morphostructure were observed by HEstaining. The expression and distribution of Cx43protein were detected byimmunohistochemistry staining and the expressions of Cx43mRNA were measured byreverse transcription polymerase chain reaction (RT-PCR).Results (1) Echocardiography showed by the end of the experiment, compared withthe AT group and the So group, LVPWs、LVPWd、IVSs and IVSd were increasedsignificantly in the AC group(P<0.05), and there is no parameter difference betweenthe AT and the SO group(P>0.05);(2)Cardiac electrophysiology showed that the QTdispersion of the AC group was significantly longer than that of the SO group and theAT group (P<0.05), but there was not significantly different between the SO groupand the AT group (P>0.05);(3) HE staining、TDM and LVW/BW: compared with theAT group and the SO group, the cardiomyocytes showed significant hypertrophy anddisordered arrangement, and TDM and LVW/BW were significantly increased in theAC group (P<0.05), but there was not significantly different between the SO groupand the AT group(P>0.05), and the cardiomyocytes were arranged regularly;(4)Immunohistochemistry analysis showed that the Cx43positive spots distributedregularly in the SO group and the AT group, but disorderly in the AC group. Theexpression of Cx43protein in the SO group and the AT group were significantlyincreased than that of the AC group (P<0.05), but there was no significant differencebetween the SO group and the AT group (P>0.05);(5) RT-PCR showed that theCx43mRNA expression in the AC group was decreased evidently than that of the SOgroup and the AT group (P<0.05). There was no parameter difference between the ATgroup and the SO group (P>0.05). Conclusion Tongxinluo can prevent cardiac hypertrophy induced by pressureoverload, shorten QT dispersion of cardiac hypertrophy rat and attenuate the action ofCx43remodeling of hypertrophied myocardium.