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ABSTRACT: The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced
by the abdominal aorta partial coarctation were investigated. Rat models of myocardial hypertrophy were established by using
abdominal aorta partial coarctation method. Forty-eight rats were randomly divided into sham group (S group), model group
(M group), valsartan treatment group (X group), low-dose tanshinone treatment group (LD group), medium-dose tanshinone treatment
group (MD group), and high-dose tanshinone treatment group (HD group) (n = 8 in each group). Left ventricular mass index (LVMI), left ventricular posterior wall (LVPW), and septal thickness (IVS)
were detected by high frequency ultrasonography. Myocardial fiber diameter (MFD) was examined by Hematoxylin-Eosin (HE) staining,
and the contents of phosphorylated protein kinase B (p-Akt) and p-Gsk3β in myocardium were assayed by Western blot. The results
showed that compared with S group, the values of LVMI, LVPW, IVS and MFD were increased in other groups (P<0.05), and the contents of p-Akt, and p-Gsk3β were also increased in other groups. As compared with MD group, the values
of LVMI, LVPW, IVS and MFD were decreased in all treatment groups (P<0.05), and the contents of p-Akt, and p-Gsk3β were also decreased in all treatment groups. However, there were no significant
differences among LD, MD, and HD groups (P>0.05), and there were no significant differences between X group and tanshinone treatment groups (P>0.05). It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.
Frontiers of Medicine in China 04/2012; 3(4):431-436.
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ABSTRACT: To explore the protective effect of sodium tanshinone IIA sulfonate (STS) on microcirculatory disturbance of small intestine in rats with sepsis, and the possible mechanism, a rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats were randomly divided into 3 groups: sham operated group (S), sepsis group (CLP) and STS treatment group (STS). STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed. The levels of tumor necrosis factor-α (TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay (ELISA). The expression of intercellular adhesion molecule-1 (ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot, that of nuclear factor κB (NF-κB) and tissue factor (TF) by using Western blot, and the levels of NF-κB mRNA expression by using RT-PCR respectively. The microcirculatory disturbance of the intestine was aggravated after CLP. The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group. The expression levels of NF-κB p65, ICAM-1, TF and TNF-α were upregulaed after CLP (P<0.01). STS post-treatment could ameliorate the microcirculatory disturbance, attenuate the injury of the intestinal tissues induced by CLP, and decrease the levels of NF-κB, ICAM-1, TF and TNF-α (P<0.01). It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.
Journal of Huazhong University of Science and Technology 08/2011; 31(4):441-5. · 0.38 Impact Factor
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ABSTRACT: Tanshinone IIA, one of the main active components from the Chinese herb Danshen, is widely used to treat cardiovascular diseases in Asian countries, especially in China. To further elucidate its heart rate-reducing and anti-ischemic mechanisms, here we investigated the effects of tanshinone IIA on hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels expressed in Xenopus oocytes using two-electrode voltage clamp techniques. When applied to the extracellular solution, 100 microM tanshinone IIA caused a slowing of activation and deactivation and an increase of minimum open probabilities (from 0.06 +/- 0.01 to 0.29 +/- 0.03, P<0.05) in HCN2 channels without shifting the voltage dependence of channel activation. Tanshinone IIA potently enhanced the amplitude of voltage-independent current (instantaneous current) of HCN2 at -90 mV in a concentration-dependent manner with an EC(50) of 107 microM. Similar but 2.3-fold less sensitivity to tanshinone IIA was observed in the HCN1 subtype. More significant effect on HCN2 and MiRP1 co-expression was observed. In conclusion, tanshinone IIA changed HCN channel gating by selectively enhancing the instantaneous current (one population of HCN channels), which resulted in the corresponding increment of minimum open probabilities, slowing channel activation and deactivation processes with little effect on the voltage-dependent current (another population of HCN channels).
Journal of Pharmacological Sciences 07/2009; 110(3):381-8. · 2.08 Impact Factor
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Le Yang,
Xiaojing Zou,
Qiansheng Liang,
Hao Chen,
Jun Feng,
Li Yan, Zhaohua Wang,
Daixing Zhou,
Shusheng Li,
Shanglong Yao,
Zhi Zheng
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ABSTRACT: Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal- regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [(3)H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS.
Experimental and Molecular Medicine 03/2007; 39(1):65-73. · 2.48 Impact Factor
