Zhao Jingjing, Zhou Yan, Liu Huahua, Zheng Zhaohai, Liu Shuqing, Peng Jiahao, Guo Hangyuan, Tang Weiliang, Peng Fang
Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang 312000, China.
Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
Evid Based Complement Alternat Med. 2021 Mar 18;2021:6620564. doi: 10.1155/2021/6620564. eCollection 2021.
To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM).
Forty male SD rats were randomly divided into control group (control group, = 10), DCM model group (DCM group, = 10), DCM model + pioglitazone group (DCM + PLZ group, = 10), and DCM model + MTDP group (DCM + MTDP group, = 10). An intraperitoneal single injection of 65 mg/kg streptozotocin (STZ) was used to establish rat model of DCM and the rats in control group were treated with the same dose of sodium citrate buffer solution. DCM + PLZ group was treated with 3 mg/kg/d PLZ by ig after modeling, DCM + MTDP group was treated with 22 mg/kg/d MTDP by ig, and DCM group was treated with 2 ml/kg/d sodium carboxymethyl cellulose (CMC-Na) by ig. The general condition of rats was continuously observed. After intervening for 3 weeks, the random blood glucose of rats was detected by tail vein, and the echocardiography examination was performed. Blood specimens were collected from the abdominal aorta, serum nitric oxide (NO) and endothelin-1 (ET-1) were detected to estimate endothelial function, and tumor necrosis factor (TNF-), interleukin 6 (IL-6), IL-1, malondialdehyde (MDA), and superoxide dismutase (SOD) were detected to observe the changes of inflammation and oxidative stress indexes. The heart mass index (HMI) was calculated through the ratio of heart mass (HM) to the corresponding body mass (BM). Myocardial pathological tissue staining was performed.
Compared with control group, blood glucose in other three groups was higher. Left ventricular end systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) in DCM group showed a significant increase, while left ventricular ejection fraction (LVEF) and heart rate (HR) in this group displayed an obvious decrease ( < 0.01). BM and HM in DCM group exhibited a reduction, and HM/BM × 10 revealed an apparent increase ( < 0.01). The levels of serum NO and SOD were distinctly downregulated ( < 0.01), and the levels of ET-1, MDA, TNF-, IL-1, and IL-6 were remarkably upregulated ( < 0.01). Compared with DCM group, a significant decrease was observed in LVSD and LVDD in DCM + MTDP group, while LVEF and HR obviously increased ( < 0.05). BM and HM indicated an apparent increase, but HM/BM ×10 reduced distinctly ( < 0.01). The levels of serum NO and SOD were markedly upregulated ( < 0.05), and the levels of ET-1, MDA, TNF-, IL-1, and IL-6 were significantly downregulated ( < 0.05). HE staining showed that myocardial cells arranged neatly in the control group but not in the DCM group. The intercellular space between myocardial cells in DCM group increased, accompanied by damage of myocardial fibers and infiltration of inflammatory cells. Masson staining displayed an increase in interstitial collagen fibers in DCM group. Carstairs staining showed that microembolization occurred in the myocardium in DCM group, while in DCM + MTDP and DCM + PLZ groups the corresponding myocardial pathological changes were significantly improved.
MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.
探讨麝香通心滴丸（MTDP）对糖尿病性心肌病（DCM）心肌重构和微循环功能障碍的影响。
将40只雄性SD大鼠随机分为对照组（对照组，n = 10）、DCM模型组（DCM组，n = 10）、DCM模型+吡格列酮组（DCM + PLZ组，n = 10）和DCM模型+ MTDP组（DCM + MTDP组，n = 10）。采用腹腔单次注射65 mg/kg链脲佐菌素（STZ）建立大鼠DCM模型，对照组大鼠给予相同剂量的柠檬酸钠缓冲液。DCM + PLZ组造模后ig给予3 mg/kg/d PLZ，DCM + MTDP组ig给予22 mg/kg/d MTDP，DCM组ig给予2 ml/kg/d羧甲基纤维素钠（CMC-Na）。持续观察大鼠一般情况。干预3周后，尾静脉检测大鼠随机血糖，并进行超声心动图检查。采集腹主动脉血标本，检测血清一氧化氮（NO）和内皮素-1（ET-1）以评估内皮功能，检测肿瘤坏死因子（TNF-）、白细胞介素6（IL-6）、IL-1、丙二醛（MDA）和超氧化物歧化酶（SOD）以观察炎症和氧化应激指标的变化。通过心脏质量（HM）与相应体重（BM）的比值计算心脏质量指数（HMI）。进行心肌病理组织染色。
与对照组相比，其他三组血糖均升高。DCM组左心室收缩末期内径（LVSD）和左心室舒张末期内径（LVDD）显著增加，而该组左心室射血分数（LVEF）和心率（HR）明显降低（P < 0.01）。DCM组BM和HM降低，HM/BM×10明显升高（P < 0.01）。血清NO和SOD水平明显下调（P < 0.01），ET-1、MDA、TNF-、IL-1和IL-6水平显著上调（P < 0.01）。与DCM组相比，DCM + MTDP组LVSD和LVDD明显降低，LVEF和HR明显升高（P < 0.05）。BM和HM明显增加，但HM/BM×10明显降低（P < 0.01）。血清NO和SOD水平显著上调（P < 0.05），ET-1、MDA、TNF-、IL-1和IL-6水平明显下调（P < 0.05）。HE染色显示对照组心肌细胞排列整齐，DCM组则不然。DCM组心肌细胞间间隙增大，伴有心肌纤维损伤和炎症细胞浸润。Masson染色显示DCM组间质胶原纤维增多。Carstairs染色显示DCM组心肌发生微栓塞，而DCM + MTDP组和DCM + PLZ组相应心肌病理改变明显改善。
MTDP可能对DCM大鼠心肌重构和微循环功能障碍具有积极作用。
