Effect Of Shexiangbaoxinwan Pill On Myocardial Fibrosis Of Diabetic Rats

ObjectiveTo observe the effects of Shexiangbaoxinwan(SBW) on myocardial fibrosisof diabetic rats and the influence on the expression of collagen typeⅠ, AngⅡ,TGF-β1, CTGF of SBW on diabetic rat myocardium and to investigate theprossible prevention cytology mechanism of SBW on diabetic cardiomyopathyon the progress.Methods10healthy SD rats which were selected randomly were assigned to normalcontrol group (group NC),30diabetic model rats by STZ were randomlyassigned to diabetic group (group DM),and SBW low-dose and high-dosetreatment group (group SL,SH),10per group. Rats in group SL,SHwere treatedrespectively with SBW50,100mg·kg-1·d-1to gastric lavage, those in group NCand DM were treated with corresponding sodiumchloride. To test the maximumrise rate of left room pressure (dp/dtmax), the maximum decline rate of left roompressure (dp/dtmin), left ventricular end-systolic pressure (LVESP), leftventricular end-diastolic pressure (LVEDP) at the12th weekend, body weight,heart weight and left ventricular mass were weighted, The ratio of heart weightto body weight (H/B) and left ventricular mass index (LVMI) were calculated;The myocardial interstitial collagen volume fraction (CVF) were Measured withMasson methods; The ultrastructure of myocardial cell was observed withelectron micscope; The concentration of AngiotensinⅡ (Ang Ⅱ) of regionalmyocardium were determined by radioimmunoassay; Detect the qualitation and semiquantitative expressions of collagen typeⅠ, TGF-β1and CTGF inmyocardium by immunohistochemical method and semiquantitative expressionsby western blot method.ResultsThe H/B and LVMI of group DM,SL,SHwere elevated statisically significantcompared with the group NC; the H/B and LVMI of group SL,SHwere declinedstatisically significant Compared with the group DM; There were statisticalsignificance between the group SL,SH.Heart function index: The dp/dtmax, dp/dtmin, LVESP of group DM,SL,SHwere declined significantly, the LVEDP were elevated significantly comparedwith the group NC; The dp/dtmax, dp/dtmin, LVESP of group SL,SHwereelevated, the LVEDP were declined compared with the group DM; There werestatistical significance between the group SL,SH.Light microscope: HE methods: myocardial cells arranged disorders, orminor myocardial necrosis, interstitial and interstitial collagen increased, andinterstitial fibrosis in clear, part of muscle fibers break compared with the groupNC, structural changes in group SL,SHwere improved significantly comparedwith group DM; The collagen tissue of myocardial cells of group DM,SL,SHincreased significantly, thick collagen connected into a network, arrangeddisorderly, distributed unevenly, around the myocardial cells and smallPerivascular compared with the group NC; However, structural changes ingroup SL,SHwere improved significantly compared with group DM.Electron microscope: The cardiac muscle fibers of group DM,SL,SHarranged disorderly, local collagen fibers broke, dissolved, the number ofmitochondrion with compensatory hyperplasia and swelling were increasedsignificantly compared with the group NC; However, structural changes in groupSL,SHunder electron microscope were improved significantly compared withgroup DM. Radioimmunoassay method for measuring the concentration of Ang Ⅱ: Theconcentration of Ang Ⅱof group DM,SL,SHwere elevated significantly comparedwith the group NC (P <0.01); The concentration of Ang Ⅱof group SL,SHweredeclined significantly compared with the group DM (P <0.01); There werestatistical significance between the group SL,SH.The expressions of proteins by immunohistochemical method and westernblot method: The qualitation and semiquantitative expression of collagen typeⅠ,TGF-β1,CTGF in group DM,SL,SHwere elevated statisically significantcompared with group NC (P <0.01); but were declined statisically significantcompared with group DM; they had statistical significance between groupSL,SH(P <0.01).Conclusion1、Diabetic rats at the12th weekend were observed the damage of cardiacultramicrostructure and heart function.2、SWB can improve cardiac ultramicrostructure and heart function.3、The inhibition of SBW on myocardial fibrosis of diabetic rats may berelated to reducing the expression of Ang Ⅱ, TGF-β1and CTGF in myocardialtissue.4、 The effects of SBW on myocardial fibrosis of diabetic rats havedose-dependence.