Effects of Aconitum coreanum polysaccharides on TGF-β induced endothelial-mesenchymal transition and its mechanisms / 中国药理学通报

Aim To investigate the protective effect of Aconitum coreanum polysaccharides ( ACP) on TGF-β induced endothelial-mesenchymal transition ( EndMT) and its underlying mechanism. Methods HUVECs EndMT model was reproduced by 10 μg·L-1 TGF-β cultured for 72 h in vitro. The effect of ACP(50, 100, 200 mg·L-1) at various concentrations on TGF-β in-duced EndMT of HUVECs was explored. CCK8 assay was employed to detect the cell viability of HUVECs stimulated by ACP. Scratch test was used to analyze the migration ability of cells. The expressions of CD31, α-SMA, Smad2/3, p-Smad2/3 were deter-mined by Western blot. Results CCK-8 assay showed that various concentrations of ACP could promote HU-VECs viability obviously by 10 μg·L-1 TGF-β cul- tured for 36 h. Scratch test showed that TGF-β en-hanced transfer ability of HUVECs significantly, while this case was apparently reversed under the costimula-tion of TGF-β and ACP. Western blot showed that CD31 expression decreased significantly, and the ex-pressions of α-SMA, p-Smad2, p-Smad3 increased significantly, and this phenomenon could be regressed with ACP. Conclusion ACP can inhibit EndMT in HUVECs induced by TGF-β clearly, and the mecha-nism is related to down-regulation of p-Smad2, p-Smad3.

Effect of tianma gouteng decoction on the endothelial function and the renal protein expression in spontaneously hypertensive rats / 中国中西医结合杂志

<p><b>OJECTIVE</b>To observe the effect of tianma gouteng decoction (TGD) on the endothelial function and the renal protein expression of spontaneously hypertensive rats, and to analyze its possible mechanism.</p><p><b>METHODS</b>Totally 18 6-week-old SHR were randomly divided into 3 groups according to randomized block design, the SHR control group, the TGD group, and the captopril group, 6 in each group. Meanwhile, Wistar Kyoto (WKY) rats of the same age were recruited as a WKY control group. Rats in the TGD group were administered with TGD at the daily dose of 10. 260 g/kg. Rats in the captopril group were administered with captopril at the daily dose of 3. 375 g/kg. 2 mL/100 g distilled water was administered to rats in the SHR control group and the WKY control group. All medication was performed by gastrogavage once per day till rats were 24 weeks old. Changes of blood pressure were measured once per two weeks. The relaxation of the thoracic aorta and the superior mesenteric artery was determined by vascular ring in vitro to reflect the endothelial function. The total renal protein was separated by two-dimensional electrophoresis (2-DE). The significantly deviated protein was verified by Western blot.</p><p><b>RESULTS</b>(1) Compared with the SHR control group, blood pressure was significantly lowered in rats (10 - 24 weeks old) of the captopril group (P <0.01, P <0.05). The hypotensive effect of TGD was obvious at the beginning of hypertension (10 -12 weeks) (P <0. 01). But along with the progression of hypertension, its hypotensive effect was not obvious (P>0. 05). (2) Compared with the SHR control group, the relaxation of the superior mesenteric artery was obviously improved in the TGD group (P <0. 05); the relaxation of the thoracic aorta and the superior mesenteric artery was obviously superior in the WKY control group (P <0. 01, P <0. 05). But there was no statistical difference in each relaxation index between the captopril group and the SHR control group (P >0. 05).(3) RESULTS: of 2-DE found 16 significantly differential renal protein, mainly involved nitric oxide (NO) system, oxidative stress, and cytoskeleton-related proteins. Results of Western blot showed that TGD could significantly improve expressions of Cu-Zn superoxide dismutase (SOD), N(G, N(G)-dimethylarginine dimethylaminohydrolase 2 (DDAH2), and pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) (P <0. 05).</p><p><b>CONCLUSION</b>GTD could protect the endothelial function of the superior mesenteric artery in SHR, and its intervention mechanism of hypertension induced early renal injury might be relevant to regulating the NO system and antioxidative stress.</p>

Effect of banxia baizhu tianma decoction on the vascular endothelial function of spontaneous hypertensive rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the vascular endothelial function recovery and its mechanism of Banxia Baizhu Tianma Decoction (BBTD).</p><p><b>METHODS</b>54 SH rats were randomly divided into three groups: the blank control group, BBTD group and Captopril treatment group. BBTD (at the daily dose of 4. 320 g crude drug/kg) and Captopril (at the daily dose of 3.375 g/kg) was administered from the 7th week to the 24th week. Another eighteen Wistar-Kyoto rats of the same ages were taken as the control. Medication was discontinued and effects were observed until the 32nd week. The blood pressure was determined by arterial carotis cannula. The concentration of serum NO2(-) and total anti-oxidation were determined by Griess and fluorescence recovery after photobleaching (FRAP). The acetylcholine (Ach)-dependent relaxation of superior mesenteric artery was detected using in vitro vascular ring. The mRNA expressions of IL-1, IL-6 and iNOS were detected by Real-time PCR at the 18th, 24th, and 32nd week.</p><p><b>RESULTS</b>BBTD could significantly lower blood pressure of SHR and the concentration of serum NO2(-) at the 18th and 24th week (P<0.05). The total anti-oxidation of SH rats increased at the 18th week (P<0.01), and ACh-dependent relaxation of superior mesenteric artery increased at the 24th week. The mRNA expressions of IL-1 was markedly suppressed by BBTD at the 18th, 24th, and 32nd week (P<0.05), while IL-6 and iNOS mRNA expression were significantly lowered only at the 32nd week (P< 0.01). Captopril could significantly lower blood pressure of SHR at the 18th and 24th week (P<0.05). It significantly increased the total anti-oxidation of SH rats at the 18th week (P<0.01). However, it could not increase ACh-dependent relaxation of superior mesenteric artery and regulate the concentration of NO2(-) at the 18th, 24th, and 32nd week. The mRNA expression of iNOS was markedly suppressed by Captopril at the 24th and 32nd week, while mRNA expressions of IL-1 and IL-6 were significantly lower only at the 32nd week (P<0.01).</p><p><b>CONCLUSIONS</b>BBTD showed similar effect in decreasing the blood pressure to captopril, but it showed better effect in improving the mesenteric endothelial dysfunction of SHR, which may be associated with its inhibition on NO and IL-1 expression, and improvement of the oxidative stress state.</p>

Effect of banxia baizhu tianma decoction on the left ventricular hypertrophy of hypertrophied myocardium in spontaneously hypertensive rat / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the changes in renin angiotensin system (RAS) in hypertrophied myocardium of spontaneous hypertensive rat (SHR), and the effect of Banxia Baizhu Tianma Decoction (BBTD) on the changes in haemodynamic parameters and mRNA of signaling molecules of RAS at different periods.</p><p><b>METHODS</b>Fifty-four male SHRs of 6 weeks old were randomly and equally divided into three groups: the untreated control group, the test group, and the positive control group, and they were treated respectively with distilled water, BBTD and captopril by dissolving in equal volume of water administrated via gavage for 18 weeks. Besides, 18 age matched Wistar-Kyoto (WKY) rats treated with distilled water were allocated in a normal control group. Rats were managed in batches at their age of 18, 24, and 32 weeks old. Rat's hemodynamic parameters were measured through carotid artery catheterization, myocardial pathology was observed, and their mRNA expressions of angiotensin (AGT), angiotensin-converting (ACE) and angiotension-converting 2 (ACE2) were determined by Real-time PCR.</p><p><b>RESULTS</b>Compared with WKY rats, the arterial pressure and left ventricular mass index (LVMI)in SHR were significantly higher at 18, 24 and 32 weeks respectively (P < 0.01); average cycle rate showed in electrocardiogram was higher (P < 0.05), though the blood stream was similar; mRNA expressions of AGT and ACE in heart tissue were markedly higher (P < 0.01), but that of ACE2 at 18 and 24 weeks were lower (P < 0.01). Compared with untreated SHR, arterial pressure at 18 and 24 weeks was lower (P < 0.05); cardiac muscle structure was improved; LVMI at 24 weeks was improved (P < 0.05); the mRNA expressions of AGT and ACE were suppressed but that of ACE2 increased at 18, 24,and 32 weeks significantly in the test group after BBTD treatment (P < 0.05).</p><p><b>CONCLUSIONS</b>Changes in RAS in the hypertrophied myocardium of SHR may be one of the molecular mechanisms for hypertension leading to left ventricular hypertrophy. BBTD can improve the hemodynamic parameters, regulate RAS, so as to lower the arterial pressure.</p>