Shiyang Xie

Jia-Shen decoction-medicated serum inhibits angiotensin-II induced cardiac fibroblast proliferation via the TGF-β1/Smad signaling pathway

Jia-Shen decoction (JSD) is a traditional Chinese medicine, which is used widely to treat chronic heart failure. However, the underlying mechanism remains to be elucidated. The present study aimed to investigate the mechanism underlying the effects of JSD on cardiac fibroblast (CF) proliferation and differentiation. The CFs were obtained from the hearts of neonatal (1-3-day old) Sprague-Dawley rats and treated with JSD-medicated serum (JSDS) with or without angiotensin II (Ang II). Cell proliferation was assessed using Cell Counting Kit-8 reagent. In addition, the mRNA expression levels of transforming growth factor-β1 (TGF-β1) and phosphorylated small mothers against decapentaplegic (p-Smad)2/3 and their protein expression levels were analyzed. CF proliferation was significantly increased in the Ang II-treated group, compared with the control group (P<0.05). The expression levels of collagen, α-smooth muscle actin, TGF-β1 and p-Smad2/3 were also increased in the Ang II-treated group (P<0.05). Following JSDS treatment, the increased levels of collagen and cell proliferation were inhibited, and the increased expression levels of p-Smad2 and p-Smad3 were also inhibited (P<0.05). These data suggested that JSDS may inhibit CF proliferation via attenuating the TGF-β1/Smad signaling pathway.

Protective effects of Jiashen Prescription (加参方) on myocardial infarction in rats

ObjectiveTo evaluate the effects of Jiashen Prescription (加参方, JSP) on myocardial infarction (MI) size and cardiac function at the early stage of MI in rats.MethodsOne hundred male Sprague-Dawley rats were subjected to sham-operation or MI induced by ligating the left anterior descending coronary artery. The rats with MI were treated with vehicle, JSP 3 and 6 g/(kg·d), or losartan 10 mg/(kg·d) for 1 week.ResultsCompared with the vehicle-treated MI rats, 6 g/(kg·d) JSP reduced MI size 3 days after MI (P<0.05), and attenuated the MI-induced increases in left ventricular end-diastolic and end-systolic dimension and decreases in fractional shortening and ejection fraction 1 week after MI (P<0.05). In addition, 6 g/(kg·d) JSP and losartan were equally effective in reducing MI size and enhancing cardiac functional recovery.ConclusionJSP reduces MI size and improves cardiac function after MI, suggesting that JSP has potential as a therapy for MI.

GW24-e2125 PROTECTIVE EFFECTS OF A PRESCRIPTION OF JIASHEN ON MYOCARDIAL INFARCTION VIA INHIBITION OF INFLAMMATION IN RATS

Objectives To determine the role of inflammation in myocardial protection induced by a prescription of Jiashen (PJS) in the early period of myocardial infarction (MI) in rats. Methods MI was induced by the ligation of left anterior descending coronary artery in Sprague-Dawley rats. The rats were divided into five groups: sham-operated group; MI + vehicle group; PJS-3g (3 g/kg/day) group; PJS-6g (6g/kg/day) group and losartan (10 mg/kg/day) group. Infarct size (IS) was determined by Evans blue and 2,3,5-Triphenyltetrazolium chloride (TTC) 3 days after MI; the left ventricular structure and function were measured by echocardiography performed 1 week after MI; and myocardial inflammatory mediators including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1) were measured by ELISA. Results Compared with the MI + vehicle group, treatment with PJS at the dose of 6 g/kg/day reduced myocardial IS (P < 0.05), left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) (P < 0.01), and enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P < 0.01). Compared with the MI + vehicle group, administration of PJS dose-dependently attenuated the increased levels of TNF-α, IL-1β and MCP-1 in ischaemic myocardium (P < 0.01). PJS at the dose of 6 g/kg/day had equally effectiveness with losartan. Conclusions Our studies showed that consistent with losartan-induced cardioprotection, PJS administered after MI reduced myocaidial IS and improved cardiac function that was associated with the decreased inflammatory mediators. The data indicate that PJS exert its cardioprotection possibly via inhibiting inflammatory response.

GW24-e3612 Effects of prescription of Jiashen on ventricular remodelling and infiltration of monocyte/macrophages in the early period after myocardial infarction in rats

Objectives This study was designed to test the hypothesis that PJS modulates inflammatory processes to prevent cardiac functional deterioration and reduce ventricular remodelling after MI. Methods Male Sprague-Dawley rats (9-10 weeks) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 1 and 4 weeks. The rats were divided into five groups: sham, MI, PJS (3 g/kg/day), PJS (6 g/kg/day), and losartan (an AT1 antagonist, 10 mg/kg/day). The vehicle, PJS, or losartan was given by oral gavage once a day after MI. Cardiac functions were determined by echocardiographic measurements at 1 and 4 weeks after MI. Fibrinogen at the site of infarction and in ischaemic myocardium were determined by Masson staining. Results of quantitative analysis were used to detect the level of hydroxyproline. Monocyte/macrophages expression was detected by immunohistochemistry staining and quantitative analysis. Results 1) The echocardiographic measurement showed that Both LVEDd and LVESd in the PJS-6 and Losartan groups were significantly shorter than in the MI group at both week 1 and week 4 post-MI. Both FS and EF were well-maintained in the PJS-6 and Losartan groups than in the MI group at both week 1 and week 4 post-MI. 2) Masson trichrome staining of cardiac sections: At 1 and 4 weeks after myocardial infarction, fibrinogen proliferation was much more obvious in MI group than in sham operation group.a detectable reduction of fibrinogen with PJS-6 and Losartan groups at the site of infarction was not found but was reduced at ischaemic sites. Results of quantitative analysis shows: compared to the MI group, the PJS-6 and losartan groups significantly decrease at both the infarction and ischaemia areas the level of fibrinogen. 3) Immunohistochemical results of monocyte/macrophages shows: At 1 and 4 weeks after myocardial infarction, monocyte/macrophages was much more obvious in MI group than in sham operation group compared to the MI group, the PJS-6 and losartan groups significantly decrease at both the infarction and ischaemia areas of monocyte/macrophages. Conclusions Our studies demonstrate that the PJS improves cardiac function, inhibits cardiac remodelling and suppresses infiltration of monocyte/macrophages after myocardial infarction. The data indicate that PJS inhibits its ventricular remodelling possibly via inhibiting infiltration of monocyte/macrophages. The results suggest that PJS may have a promising potential for the prevention and treatment of MI.

GW24-e3626 Effects of prescription of Jiashen on TGF-beta/Smads pathway after myocardial infarction in rats

Objectives This study was designed to study the effect of PJS on TGF-β/Smads pathway after MI in rats. Methods Male Sprague-Dawley rats (9-10 weeks) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 1 and 4 weeks. The rats were divided into five groups: sham, MI, PJS (3 g/kg/day), PJS (6 g/kg/day), and losartan (an AT1 antagonist, 10 mg/kg/day). The vehicle, PJS, or losartan was given by oral gavage once a day after MI. The expressions of TGF-β1, p-smad2, p-smad3 in the myocardium were assayed using Western-blot at 1 week or 4 weeks after MI. Results At 1 week after MI, administration of PJS (3 or 6 g/kg/day) attenuated the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 1.21 ± 0.06 or 1.06 ± 0.03 vs.1.37 ± 0.09,p < 0.0 5; p-smad 2: 1.88 ± 0.04 or 1.52 ± 0.11 vs. 2.09 ± 0.24,p < 0.05; p-smad3: 0.83 ± 0.01 or 0.5 ± 0.02 vs. 1.05 ± 0.120, p < 0.05). The greater effect was achieved at a dose of 6 g/kg/day. Losartan treatment also inhibited the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 0.58 ± 0.03 vs. 1.37 ± 0.09, P < 0.05; p-smad2: 1.27 ± 0.02 vs. 2.09 ± 0.24, P < 0.05; p-smad3: 0.23 ± 0.01 vs.1.05 ± 0.12, P < 0.05). At 4 week after MI, administration of PJS (3 or 6 g/kg/day) attenuated the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β: 0.58 ± 0.03 or 0.69 ± 0.02 vs. 0.78 ± 0.01, p < 0.0 5; p-smad 2: 0.57 ± 0.04 or 0.77 ± 0.02 vs. 0.88 ± 0.05, p < 0.05; p-smad3: 0.50 ± 0.01 or 0.65 ± 0.02 vs. 0.78 ± 0.01, p < 0.05). The greater effect was achieved at a dose of 6 g/kg/day. Losartan treatment also inhibited the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 0.42 ± 0.01vs. 0.78 ± 0.01, P < 0.05; p-smad2: 0.24 ± 0.57 vs. 0.88 ± 0.05, P < 0.05; p-smad3: 0.39 ± 1.87 vs. 0.78 ± 0.01, P < 0.05). Conclusions Our studies showed PJS administered can significantly inhibite TGF-β/Smads pathway after MI in rats. The data indicate that PJS improves cardiac remodelling possibly via inhibiting TGF-β/Smads pathway. The results suggest that PJS may have a promising potential for the prevention and treatment of MI.

PROTECTIVE EFFECTS OF OPTIMAL PRESCRIPTION OF JIASHEN ON MYOCARDIAL INFARCTION IN RATS

Objectives This study was designed to test the hypothesis that OPJSH modulates inflammatory processes to prevent cardiac functional deterioration and reduce myocardial infarct size (IS) after MI. Methods Male Sprague-Dawley rats (9–10 weeks) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 1 week. The rats were divided into five groups: sham, MI, OPJSH (3 g/kg/day), OPJSH (6 g/kg/day), and losartan (an AT1 antagonist, 10 mg/kg/day). The vehicle, OPJSH, or losartan was given by oral gavage once a day after MI. Both IS and cardiac function were determined using TTC staining and Echocardiography at 1 week after MI, respectively. The levels of cytokines, including TNF-α, IL-1β; and chemokine, including MCP-1 in the myocardium were assayed using ELISA at 1 week after MI. Results OPJSH (3 or 6 g/kg/day) administered after MI reduced IS compared with MI group (39±9%, 33±13% vs 55±8%, p<0.05) with the greater effect at a dose of 6 g/kg/day. Administration of losartan also reduced IS compared with MI group (39±6% vs 55±8%, p<0.05). Compared with MI group, administration of OPJSH (3 or 6 g/kg/day) improved cardiac function as evidence by partially preventing the increases in LVEDD (0.87±0.15 vs 0.72±0.13 or 0.65±0.13 cm, p<0.05) and LVESD (0.72±0.15 vs 0.55±0.16 or 0.45±0.16 cm, p<0.05), and the decreases in LVEF (39.0±8.1% vs 53.6±20.1% or 69.4±15.6%, p<0.05) and LVFS (16.3±3.8% vs 25.6±12.8% or 36.5±13.9%, p<0.05), the greater effect was achieved at a dose of 6 g/kg/day. Losartan treatment also improved cardiac function compared with MI group as shown by the normalisation of LVEDD (0.49±0.08 vs 0.87±0.15 cm, p<0.05) and LVESD (0.30±0.06 vs 0.72±0.15 cm, p<0.05), and attenuating the decreases in LVEF (75.4±4.9% vs 39.0±8.06%, p<0.05) and LVFS (38.6±4.2% vs 16.3±3.8%, p<0.05). Additionally, administration of OPJSH (3 or 6 g/kg/day) attenuated the increases in myocardial levels of cytokine and chemokine compared with MI group (TNF-α: 4.71±1.14 or 3.97±0.72 vs 5.05±1.01 pg/mg protein, p<0.05; IL-1β: 10.18±1.36 or 7.47±2.50 vs 13.82±2.11 pg/mg protein, p<0.05; MCP-1: 8.78±1.12 or 7.52±0.63 vs 12.70±1.46 pg/mg protein, p<0.05). Losartan treatment also inhibited the increases in myocardial levels of cytokine and chemokine compared with MI group (TNF-α: 3.53±0.73 vs 5.05±1.01 pg/mg protein, p<0.05; IL-1β: 8.36±0.57 vs 13.83±2.11 pg/mg protein, p<0.05; MCP-1: 9.46±1.87 vs 12.70±1.46 pg/mg protein, p<0.05). Conclusions Our studies showed that consistent with losartan-induced cardioprotection, OPJSH administered after MI reduced myocardial IS and improved cardiac function that was associated the decreases in myocardial levels of cytokine and chemokine. The data indicate that OPJSH exert its cardioprotection possibly via inhibiting inflammatory response. The results suggest that OPJSH may have a promising potential for the prevention and treatment of MI.