| Clinical observation of hypertensive patients with left ventricular hypertrophy and Blood Stasis Syndrome treating with salvianolateObjective: Treating the hypertensive patients with left ventricular hypertrophy and Blood Stasis Syndrome with salvianolate,to see whether salvianolate has protective effect on this kind of patients and whether salvianolate can improve blood Lipid,blood flow and rheology,MMP-3,TIMP-1 and other things.Material and method: The patients went to Jinzhou Medical University first affilitated hospital for treatment during 2015-9 and 2016-12.80 examples of hypertensive patients with left ventricular hypertrophy and Blood Stasis Syndrome,between the age of 18 and 75 years old,were divided into two group: control group and Salvia Miltiorrhiza group.All of the patients have the character of blood stasis pattern and cardiac hypertrophy.The control group is treated with irbesartan 0.15 g /once a day;the Salvia Miltiorrhiza group is treated with irbesartan 0.15g/once a day together with Salvianolate injection 200 mg /per day,intravenous injection.If the blood pressure does not reach the target,increase the doses of irbesartan to 0.3g/once a day.The course of treatment is 14 days.The symptoms and signs score is recorded,also the age,gender,height and weight were recorded,take the blood pressure every day,the serum level of MMP-3,TIMP-1,blood Lipid,blood flow and rheology,glucose,liver function and kidney function were all measured.Results: 1.The total scores on symptoms and signs(the lower the better)in two groups were recorded.The scores decrease significantly after treatment,there were significantly differences.Between two groups,the scores of the Salvia Miltiorrhiza group were lower than that of the control group.The symptoms and signs were significantly improved in the Salvia Miltiorrhiza group after the treatment of salvianolate.Some symptoms and signs like headache,dizziness, im eyesight,constriction in the chest,pain in the chest and so on were improved significantly.The differences were significantly.As to the blood pressure,it’s decrease significantly after treatment,there was significantly difference.While there was no significant difference between the control group and Salvia Miltiorrhiza group after treatment.No important side effects and toxic reactions were found in two groups.2.The blood viscosity and blood lipid were get better in two groups after treatment.The blood viscosity and blood lipid were decreased significantly in Salvia Miltiorrhiza group then in control group after treatment,there was significantly difference(P<0.05).The whole blood viscosity(low shearing),whole blood viscosity(high shearing),whole blood reduced viscosity(low shearing),whole blood reduced viscosity(high shearing)and Plasma viscosity were 17.27±0.61 m Pa.s,4.23±0.28 m Pa.s,44.26±0.89 m Pa.s,8.93±1.31 m Pa.s and 1.66±0.03 m Pa.s respectively in Salvia Miltiorrhiza group,while in control group the whole blood viscosity(low shearing),whole blood viscosity(high shearing),whole blood reduced viscosity(low shearing),whole blood reduced viscosity(high shearing)and Plasma viscosity were 17.52±0.50 m Pa.s,4.37±0.31 m Pa.s,44.79±1.04 m Pa.s,9.36±0.23 m Pa.s and 1.67 ± 0.03 m Pa.s respectively.The blood viscosity were decreased significantly after the treatment of Salvianolate.TG,TC and LDL-C were 1.77±0.44 mmol/L,5.10±0.42 mmol/L,3.02±0.21 mmol/L respectively in Salvia Miltiorrhiza group,while in control group the TG,TC and LDL-C were 2.01±0.44 mmol/L,5.26±0.42 mmol/L,3.16±0.36 mmol/L respectively,the blood lipid were decreased significantly after the treatment of Salvianolate.TG,TC and LDL-C decreasd in Salvia Miltiorrhiza group,which were superior to those in control group(P <0.05).After treatment,MMP-3 in Salvia Miltiorrhiza group were decreased from 88.43±6.68μg.L-1 to 78.48±6.25μg.L-1,in the control group were decreased from 84.28±6.62μg.L-1 mg/L to 81.39±6.13μg.L-1.MMP-3 decreasing in Salvia Miltiorrhiza group were superior to those in control group(P <0.05).While TIMP-1 in Salvia Miltiorrhiza group were increased from 61.01±6.33μg.L-1 to 65.14±6.25μg.L-1,in control group were increased from 60.30±6.42μg.L-1 to 62.10±6.38μg.L-1.The increasing of TIMP-1 in Salvia Miltiorrhiza group were superior to those in control group(P <0.05).Conclusions:Salvianolate injection combined with usual treatment of depressurization was found to have more effects on the patients with blood stasis syndrome.It can improve symptoms and signs for the patients with hypertension.Maybe it related with promoting blood circulation remove blood stasis;decrease of blood viscosity;lower cholesterol levels and relieve cardiac fibrosis.Conclusions :Salvianolate prevents the development of myocardial hypertrophy and fibrosis in rats via TGF-β1/Smad signaling pathwayObjective: The aim of the present of study was to investigate the protective effects of salvianolate on myocardial hypertrophy and fibrosis induced by isoprenaline(ISO)in rats,and to explore the possible mechanism.And illustrate whether TGF-β1/Smad signaling pathway was contribute to the protective effect of salvianolate on ISO induced cardiac hypertrophy and fibrosis.The results of the present study will further illustrate the mechanism of the protective effects of salvianolate on myocardial diseases.Material and method: 48 Sprague-Dawley rats,weighing 200 to 220 g,were purchased from the animal center of Jinzhou medical university.The rats were housed at 12:12 light/dark cycle,temperature of 22±2℃,humidity of 65%–70%,and received standard diet and water ad libitum.After the rats were retrieved,they were fed for 3 days.The next day 48 rats were randomly divided into 6 groups:(1)Normal control group,(2)model control group,(3)salvianolate low doses group,(4)salvianolate middle doses group,(5)salvianolate high doses group,(6)propranolol group.Myocardial fibrosis model was established by subcutaneous injection of 10 mg/kg ISO in rats for 30 days except for normal control rats.Salvianolate and propanolol were administered intragastrally to rats for 30 days one day before ISO administration.At the end of experiment,all animals were anaesthetized with a 20% urethane.The right carotid were cannulated with a polyethylene catheter and then inserted into the left ventricle cavity,and the left ventricular end-diastolic pressure(LVEDP),the maximal rate of left ventricular systolic pressure(+dp/dtmax)and the maximal rate of left ventricular diastolic pressure(-dp/dtmax)were recorded by using physiological recorder.Then all animals were sacrificed by complete collection of blood and the hearts were immediately harvested,rinsed in ice-cold 0.9% Na Cl solution,dissected and weighed.The left ventricular index and the heart weight index were determined by weighing the body weight,the left ventricular weight and the whole heart weight;The content of hydroxyproline(Hyp)was assayed by ELASA kit;The histopathological change of myocardial tissue was examined by HE staining;Collagen volume fraction(CVF)was determined by picrosirius red staining;The m RNA expression of transforming growth factor-β1(TGF-β1)was determined by RT-PCR,the protein expression of TGF-β1 was determined by immunohistochemistry;The protein expressions of Smad2/3 and Smad7 were determined by western blot.Results: Compared with control group,the LVEDP decreased and +dp/dtmax and +dp/dtmax were increased,which indicating diastolic dysfunction induced by ISO.Beside,Compared with control group the left ventricular index and the heart weight index were significantly increased,and the content of Hyp were increased by 63.6%,the content of collagen and collagen volume fraction were increased.These results indicated that cardiac fibrosis was established induced by ISO.At the same time,the results from RT-PCR showed that the m RNA expression of TGF-β1 was increased compared with control group.The results from immunohistochemistry showed that the myocardial TGF-β1 expression was increased compared with control group.In addition,western bolt showed that the protein level of Smad2/3 was increased and the expression of Smad7 was decreased compared with control group.The results indicated that TGF-β1/ smad signaling pathway was up-regulated by ISO.In the present study,different doses of salvianolate and propranolol were used before ISO administration.As our expected,compared with ISO group,the LVEDP decreased and the +dp/dtmax and-dp/dtmax were decreased in medium and high dose salvianolate group,which indicated that salvianolate could improved the cardiac function induced by ISO.What is more, the left ventricular index and the heart weight index were significantly decreased in salvianolate treatment group.Salvianolate treatment also decreased the content of Hyp which increased by ISO.HE staining showed that salvianolate treatment attenuated myocardial hypertrophy and decreased the production of myocardial fibrosis.Picrosirius red staining showed that the collagen volume fraction were decreased in salvianolate treatment group.Further studies showed that the protein level of TGF-β1 and Smad2/3 were decreased and the Smad7 expression was increased in high and medium dose of salvianolate groups.Conclusion: Salvianolate could attenuate myocardial fibrosis induced by ISO via TGF-β1 / Smad signaling pathway. |
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