Effect of Musk Tongxin Dropping Pill on Myocardial Remodeling and Microcirculation Dysfunction in Diabetic Cardiomyopathy.

OBJECTIVE: To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM). METHODS: Forty male SD rats were randomly divided into control group (control group, n = 10), DCM model group (DCM group, n = 10), DCM model + pioglitazone group (DCM + PLZ group, n = 10), and DCM model + MTDP group (DCM + MTDP group, n = 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 α (TNF-α), interleukin 6 (IL-6), IL-1ß, 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. RESULTS: 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 (P < 0.01). BM and HM in DCM group exhibited a reduction, and HM/BM × 103 revealed an apparent increase (P < 0.01). The levels of serum NO and SOD were distinctly downregulated (P < 0.01), and the levels of ET-1, MDA, TNF-α, IL-1ß, and IL-6 were remarkably upregulated (P < 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 (P < 0.05). BM and HM indicated an apparent increase, but HM/BM ×103 reduced distinctly (P < 0.01). The levels of serum NO and SOD were markedly upregulated (P < 0.05), and the levels of ET-1, MDA, TNF-α, IL-1ß, and IL-6 were significantly downregulated (P < 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. CONCLUSIONS: MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.

Shexiang Tongxin dropping pill protects against sodium laurate-induced coronary microcirculatory dysfunction in rats.

OBJECTIVE: To investigate the protective effects of Shexiang Tongxin dropping pill (, STDP) in a rat model of coronary microcirculatory dysfunction (CMD). METHODS: Sprague-Dawley rats were allocated randomly into four groups: sham, CMD model, STDP, and nicorandil. After 4 weeks of treatment, CMD was induced by injection of sodium laurate (0.2 mL, 2 g/L) into the left ventricle while obstructing the ascending aorta. Rats in the sham group underwent an identical surgical procedure but were administered physiological (0.9% ) saline (0.2 mL). Twenty-four hours after surgery, blood samples were collected for biochemical analyses and enzyme-linked immunosorbent assays. Heart tissues were removed for histopathology staining; apoptosis and inflammatory cytokines were examined by Western blotting. RESULTS: The STDP group had a lower level of creatine kinase-myocardial band, lactate dehydrogenase, and cardiac troponin-I than that in the CMD model group. Infiltration of inflammatory cells, myocardial ischaemia, and microthrombosis were relieved in the STDP group compared with CMD model group. Levels of endothelin-1, nuclear factor-kappa B, tumour necrosis factor-α, interleukin-6, interleukin-1ß, malondialdehyde, B-cell lymphoma (Bcl)-2-associated X protein, and caspase-3 were lower, and levels of nitric oxide, Bcl-2, and superoxide dismutase were higher, in the STDP group in comparison with the CMD model group. CONCLUSION: STDP pretreatment improved the CMD induced by sodium laurate via anti-inflammatory, anti-apoptosis, and anti-oxidant mechanisms.

The Role of Xuefu Zhuyu Decoction in Prevention of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention.

OBJECTIVE: This study aimed to investigate the effect of Xuefu Zhuyu decoction on preventing contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). METHODS: A total of 256 patients undergoing selective PCI for coronary artery disease were consecutively enrolled and randomly divided into two groups: Group A (n = 126) and Group B (n = 130). Before and after PCI, all patients routinely received antiplatelet aggregation therapy, antilipidemic therapy, and hydration therapy. Besides routine therapy, patients in Group B received Xuefu Zhuyu decoction from 3 days before PCI to 3 days after PCI. Serum creatinine (Scr), estimated glomerular filtration rate (eGFR), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured, respectively, at baseline (72 h before PCI) and at 24, 48, and 72 h after PCI. RESULTS: Compared with Group A, Group B presented a lower fluctuation of SCr and eGFR (P < 0.01). The incidence of CIN was less in Group B. According to the definition, CIN occurred in 5 patients (2.0%) in the intervention group and 5 (4.0%) in the control group (P=0.167). In terms of oxidative stress, Group B had a lower MDA (P < 0.05), but a higher SOD (P < 0.05). CONCLUSIONS: Compared with the control group, Xuefu Zhuyu decoction intervention therapy increased the level of SOD and reduced MDA. The Xuefu Zhuyu decoction intervention group presented a higher level of eGFR at 24, 48, and 72 h after PCI in patients with coronary heart disease and a lower level of Scr. The results are propitious to prove that Xuefu Zhuyu decoction might play an antioxidative stress role in the prevention of CIN after PCI.

Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment.

BACKGROUND: Accelerated malignant behaviors induced by insufficient thermal ablation have been increasingly reported, however, the exact mechanisms are still unclear. Here, we investigated the importance of the extracellular matrix (ECM) in modulating the progression of residual hepatocellular carcinoma (HCC) after heat treatment. METHODS: Heat-exposed residual HCC cells were cultured in different ECM gels. We used basement membrane gel (Matrigel) to simulate the normal microenvironment and collagen I to model the pathological stromal ECM. The alterations of morphology and parameters of proliferation, epithelial-mesenchymal transition (EMT) and stemness were analyzed in vitro and in vivo. RESULTS: Increased collagen I deposition was observed at the periablational zone after incomplete RFA of HCC in a xenograft model. The markers of cell proliferation, EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were significantly induced by collagen I as compared to Matrigel (p values all < 0.05). Importantly, collagen I induced the activation of ERK phosphorylation in heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I-promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I promoted the in vivo tumor progression of heat-exposed residual HCC cells, and sorafenib markedly reversed the collagen I-mediated protumor effects. CONCLUSIONS: Our findings demonstrate that collagen I could enhance the aggressive progression of residual HCC cells after suboptimal heat treatment and sorafenib may be a treatment approach to thwart this process.

Folic acid delays development of atherosclerosis in low-density lipoprotein receptor-deficient mice.

Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and to elucidate the molecular processes underlying this effect. LDLR-/- mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α-actin (α-SMA) antibodies and anti-osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α-SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high-fat-fed LDLR-/- mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.