白花丹参醇提物对大鼠血栓闭塞性脉管炎的防治作用与机制研究
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摘要
目的
观察白花丹参醇提物对大鼠血栓闭塞性脉管炎(TAO)的防治作用,初步探讨其作用机制。
方法
Wistar大鼠,雄性,60只,随机分为6组,每组10只,即假手术组、模型组、三七总皂苷100mg/kg剂量组、白花丹参醇提物15g/kg剂量组、白花丹参醇提物30g/kg剂量组、白花丹参醇提物60g/kg剂量组。给药组与模型组大鼠于右下肢股动脉注射1.0mg月桂酸,假手术组同法注射等量生理盐水。注射后观察大鼠肢体病变损伤程度,主要观察患肢皮肤颜色、肿胀、坏疽和木乃伊化程度,观察时间为两周。以坏疽程度分级标准和坏疽指数(GI)记录术后1d、4d、7d、14d的病变进展,评价药物的防治效果。常规H-E染色观察大鼠肢体组织形态学改变。测定各组样本的血浆纤维蛋白原、内皮素、血栓素B2、6-酮-前列腺素F1α、血栓素B2/6-酮-前列腺素F1α比值(T/P)等血浆生化指标的变化,初步探讨其作用机制。
结果
1月桂酸1.0mg单侧股动脉注射可致大鼠TAO模型,该方法成功率高,病变进展较慢,适合实验研究所需。
2白花丹参醇提物各剂量组均对大鼠TAO模型有不同程度的防治效果,可使GI下降,延缓大鼠TAO模型的病变进程。
3白花丹参醇提物各剂量组均可使FG含量降低、ET-1含量降低、TXB2含量降低,6Keto-PGF1α含量升高,调节T/P,其中白花丹参醇提物60g/kg剂量组效果明显,与模型组相比有统计学意义(P<0.05)。PNS对大鼠TAO模型有一定的防治作用,可使GI降低,延缓病变的进行,可使FG含量降低、ET-1含量降低、TXB2含量降低,6-keto-PGF1α含量升高,调节T/P,与模型组相比有统计学意义(P<0.05)。
结论
1月桂酸1.0mg单侧股动脉注射可成功制备大鼠TAO模型,该方法成功率高,病变进展较慢,适合实验研究所需。
2白花丹参醇提物可降低大鼠TAO模型坏疽指数,延缓病变进程,对TAO有一定的防治作用,其治疗作用具有剂量依赖性。
3白花丹参醇提物可降低大鼠TAO模型血浆FG、ET-1、TXB2的含量,提高6-keto-PGF1α含量,调节T/P,这些可能与白花丹参醇提物对大鼠TAO模型发挥防治作用的机制有关。
Objective
The aim of this study was to test the preventive effect of Ethanolic extract of Salvia multiorrhiza bge.f.alba on rat models of Thromboangiitis Obliterans and the mechanism research.
Methods
60 Wistar rats (male) were randomly divided into Control group ( n=10), Model group (n=10), Panax Notoginseng Saponins 100mg/kg group (n=10), SMAE 15g/kg group (n=10), SMAE 30g/kg group (n=10), SMAE 60g/kg group (n=10). Laurate of 1.0mg was injected into the right femoral artery of every rat in the treatment groups and model group to create models. 0.1ml of Normal Saline was used in control group rats. When the injection was finished, the right limbs of rats were carefully observed. The observations of the lesion progression, which include the skin color, swelling, gangrene and mummification of the affected legs, were lasted for 2 weeks. The extent of the lesions of the first day, the fourth day, the seventh day, the fourteenth day were ranked by the Grade Evaluation of the Gangrene and the Gangrene Index (GI). The results were used to consider the preventive effect of the drugs. Got the samples of each group by the fifteenth day and determined the plasma concentration of the FG, the ET-1, the TXB2, the 6-keto-PGF1α, the ratio of TXB2 and 6-keto-PGF1α. Analyzed the mechanism by these data. Made the normal H-E staining to the pathological slice to observe the disease damage of the models and the effect of the drug treatment.
Result
1 Laurate injection of 1.0mg by the femoral artery was able to make the rat TAO model successfully and conveniently. The disease progress was slow which confirm the request of the experiment.
2 The ethanolic extracts of Salviae miltiorrhiza bge.f.alba (SMAE) were able to show the preventive effect on TAO rats. These drug extracts were able to lower the GI, slow down the disease progress.
3 The ethanolic extracts of Salviae miltiorrhiza bge.f.alba (SMAE) were able to reduce the FG, ET-1, TXB2, increased the 6-keto-PGF1α,regulate the ratio of T/P. The SMAE-H group showed a strong effect and got the statistics consequence significantly. Panax Notoginseng Saponins shows a preventive effect on TAO rats which was able to lower the GI, reduce the FG, ET-1, TXB2, increased the 6-keto-PGF1α, regulate the ratio of T/P, slow down the disease progress. The result got a statistics consequence significantly.
Conclusion
1 Laurate injection of 1.0mg by the femoral artery was able to make the rat TAO model successfully and conveniently. The disease progress was slow which confirm the request of the experiment.
2 SMAE can prevent the progress of the TAO rats, slow down the disease progress, shows the preventive effect .The effect depend on the dose of the drug positively.
3 SMA-E were able to reduce the FG, ET-1,TXB2, increase the 6-keto-PGF1αregulate the ratio of T/P, this may have connect to the mechanism of the prevention of SMAE on TAO rats.
观察白花丹参醇提物对大鼠血栓闭塞性脉管炎(TAO)的防治作用,初步探讨其作用机制。
方法
Wistar大鼠,雄性,60只,随机分为6组,每组10只,即假手术组、模型组、三七总皂苷100mg/kg剂量组、白花丹参醇提物15g/kg剂量组、白花丹参醇提物30g/kg剂量组、白花丹参醇提物60g/kg剂量组。给药组与模型组大鼠于右下肢股动脉注射1.0mg月桂酸,假手术组同法注射等量生理盐水。注射后观察大鼠肢体病变损伤程度,主要观察患肢皮肤颜色、肿胀、坏疽和木乃伊化程度,观察时间为两周。以坏疽程度分级标准和坏疽指数(GI)记录术后1d、4d、7d、14d的病变进展,评价药物的防治效果。常规H-E染色观察大鼠肢体组织形态学改变。测定各组样本的血浆纤维蛋白原、内皮素、血栓素B2、6-酮-前列腺素F1α、血栓素B2/6-酮-前列腺素F1α比值(T/P)等血浆生化指标的变化,初步探讨其作用机制。
结果
1月桂酸1.0mg单侧股动脉注射可致大鼠TAO模型,该方法成功率高,病变进展较慢,适合实验研究所需。
2白花丹参醇提物各剂量组均对大鼠TAO模型有不同程度的防治效果,可使GI下降,延缓大鼠TAO模型的病变进程。
3白花丹参醇提物各剂量组均可使FG含量降低、ET-1含量降低、TXB2含量降低,6Keto-PGF1α含量升高,调节T/P,其中白花丹参醇提物60g/kg剂量组效果明显,与模型组相比有统计学意义(P<0.05)。PNS对大鼠TAO模型有一定的防治作用,可使GI降低,延缓病变的进行,可使FG含量降低、ET-1含量降低、TXB2含量降低,6-keto-PGF1α含量升高,调节T/P,与模型组相比有统计学意义(P<0.05)。
结论
1月桂酸1.0mg单侧股动脉注射可成功制备大鼠TAO模型,该方法成功率高,病变进展较慢,适合实验研究所需。
2白花丹参醇提物可降低大鼠TAO模型坏疽指数,延缓病变进程,对TAO有一定的防治作用,其治疗作用具有剂量依赖性。
3白花丹参醇提物可降低大鼠TAO模型血浆FG、ET-1、TXB2的含量,提高6-keto-PGF1α含量,调节T/P,这些可能与白花丹参醇提物对大鼠TAO模型发挥防治作用的机制有关。
Objective
The aim of this study was to test the preventive effect of Ethanolic extract of Salvia multiorrhiza bge.f.alba on rat models of Thromboangiitis Obliterans and the mechanism research.
Methods
60 Wistar rats (male) were randomly divided into Control group ( n=10), Model group (n=10), Panax Notoginseng Saponins 100mg/kg group (n=10), SMAE 15g/kg group (n=10), SMAE 30g/kg group (n=10), SMAE 60g/kg group (n=10). Laurate of 1.0mg was injected into the right femoral artery of every rat in the treatment groups and model group to create models. 0.1ml of Normal Saline was used in control group rats. When the injection was finished, the right limbs of rats were carefully observed. The observations of the lesion progression, which include the skin color, swelling, gangrene and mummification of the affected legs, were lasted for 2 weeks. The extent of the lesions of the first day, the fourth day, the seventh day, the fourteenth day were ranked by the Grade Evaluation of the Gangrene and the Gangrene Index (GI). The results were used to consider the preventive effect of the drugs. Got the samples of each group by the fifteenth day and determined the plasma concentration of the FG, the ET-1, the TXB2, the 6-keto-PGF1α, the ratio of TXB2 and 6-keto-PGF1α. Analyzed the mechanism by these data. Made the normal H-E staining to the pathological slice to observe the disease damage of the models and the effect of the drug treatment.
Result
1 Laurate injection of 1.0mg by the femoral artery was able to make the rat TAO model successfully and conveniently. The disease progress was slow which confirm the request of the experiment.
2 The ethanolic extracts of Salviae miltiorrhiza bge.f.alba (SMAE) were able to show the preventive effect on TAO rats. These drug extracts were able to lower the GI, slow down the disease progress.
3 The ethanolic extracts of Salviae miltiorrhiza bge.f.alba (SMAE) were able to reduce the FG, ET-1, TXB2, increased the 6-keto-PGF1α,regulate the ratio of T/P. The SMAE-H group showed a strong effect and got the statistics consequence significantly. Panax Notoginseng Saponins shows a preventive effect on TAO rats which was able to lower the GI, reduce the FG, ET-1, TXB2, increased the 6-keto-PGF1α, regulate the ratio of T/P, slow down the disease progress. The result got a statistics consequence significantly.
Conclusion
1 Laurate injection of 1.0mg by the femoral artery was able to make the rat TAO model successfully and conveniently. The disease progress was slow which confirm the request of the experiment.
2 SMAE can prevent the progress of the TAO rats, slow down the disease progress, shows the preventive effect .The effect depend on the dose of the drug positively.
3 SMA-E were able to reduce the FG, ET-1,TXB2, increase the 6-keto-PGF1αregulate the ratio of T/P, this may have connect to the mechanism of the prevention of SMAE on TAO rats.
引文
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[3]任香善,宋京郁,林贞花,等.复方丹参注射液对氧化损伤血管内皮细胞的保护作用[J].延边大学医学学报,2006,29(1):30-34.
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[1]杜冠华.血管内皮细胞损伤机制及保护药物的研究[J].基础医学与临床,2004,24(3):258-263.
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[9]张启春,卞慧敏,喻丽珍,等.六味地黄方含药血清对氧化低密度脂蛋白损伤血管内皮细胞的保护作用[J].中国实验方剂学杂志,2007,13(7):31-34.
[10]戴敏,刘青云,訾晓梅.丹皮酚对高脂血症大鼠动脉内皮细胞的保护作用[J].中国中医基础医学杂志,2001,7(2):38-40
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