【摘要】：目的：探討清肝滋腎中藥(針箭顆粒Ⅱ號)通過上調(diào)內(nèi)臟脂肪組織中SIRT1的表達改善高血壓代謝紊亂的作用及機制。方法：通過高脂飲食誘導獲得自發(fā)性高血壓大鼠代謝紊亂模型。選取17只4周齡的雄性自發(fā)性高血壓大鼠(SHR),分為高脂飲食組12只和正常飲食組5只,正常飲食組給予基礎(chǔ)飼料,高脂飲食組給予高脂飼料。高脂飲食組則隨機分為針箭顆粒組6只(22.5g/kg/d,灌胃)和模型對照組6只(同體積蒸餾水,灌胃)。每周測量體重、血壓2次,根據(jù)體重改變藥物給藥量。給藥9周后處死,獲取大鼠內(nèi)臟脂肪(附睪周圍)并稱重,部分內(nèi)臟脂肪分離脂肪細胞,部分提取mRNA和蛋白,部分給予4%多聚甲醛固定HE染色。1)通過定期監(jiān)測SHR鼠血壓、體重,評估SHR大鼠代謝情況。2)采用RT-PCR和Western Blot法測定內(nèi)臟脂肪組織SIRT1 mRNA-及蛋白、裂解酶Caspase-1蛋白的表達水平,評估SIRT1表達水平和活性的變化；結(jié)果：1.清肝滋腎中藥(針箭顆粒Ⅱ號)對SHR大鼠體重的影響：基線時SHR大鼠三組之間體重無明顯差異(P0.05)；干預9周后模型組體重顯著高于對照組(P0.01),針箭顆粒組體重顯著低于模型組(P0.01),對照組與針箭顆粒組之間無顯著差異(P0.05)。2.清肝滋腎中藥(針箭顆粒Ⅱ號)對SHR大鼠血壓的影響：治療前模型組SBP高于對照組(P0.05),其余組間無顯著差異(P0.05)；三組間DBP無明顯差異(P0.05)。干預9周后,模型組與對照組之間血壓(SBP、DBP)無明顯差異,針箭顆粒組雖有下降趨勢但無統(tǒng)計學差異(P0.05)。3.清肝滋腎中藥(針箭顆粒Ⅱ號)對SHR大鼠內(nèi)臟脂肪(附睪周圍)的影響3.1各組附睪周圍脂肪重量及其體脂比的比較：1)干預9周后模型組附睪周圍脂肪含量高于對照組(P0.05),但針箭顆粒組與模型組間無明顯差異(P0.05)；2)干預9周后模型組體脂比顯著高于對照組(P0.01),但針箭顆粒組與模型組間無明顯差異(P0.05)。3.2鏡下評估附睪周圍脂肪體積及脂滴含量：模型組與對照組相比,脂肪細胞體積增大,脂滴含量增加；針箭顆粒組與模型組相比,脂肪細胞體積減小,脂滴含量減少。4.清肝滋腎中藥(針箭顆粒Ⅱ號)對SHR大鼠內(nèi)臟脂肪(附睪周圍)組織SIRT1表達及活性變化的影響4.1清肝滋腎中藥(針箭顆粒Ⅱ號)對附睪周圍脂肪組織中SIRT1 mRNA表達的影響：模型組SIRT1 mRNA的表達顯著低于對照組(P0.01),而針箭顆粒組SIRT1 mRNA的表達高于模型組(P0.05)。4.2清肝滋腎中藥(針箭顆粒Ⅱ號)對附睪周圍脂肪組織中SIRT1蛋白表達的影響：干預9周后,模型組SIRT1蛋白表達顯著低于對照組(P0.01),針箭顆粒組SIRT1蛋白表達則高于模型組(P0.05)。4.3清肝滋腎中藥(針箭顆粒Ⅱ號)對附睪周圍脂肪組織中裂解酶Caspase1蛋白表達的影響：干預9周后三組之間Caspase1蛋白表達水平無顯著差異(P0.05)。結(jié)論：1.清肝滋腎中藥(針箭顆粒Ⅱ號)可降低SHR合并代謝紊亂大鼠體重,減少內(nèi)臟脂肪的堆積。2.清肝滋腎中藥(針箭顆粒Ⅱ號)可能是通過上調(diào)內(nèi)臟脂肪組織中SIRT1的表達來改善高血壓代謝紊亂。
[Abstract]:Objective: To study the effect and mechanism of the expression of SIRT1 in visceral fat tissue by regulating the expression of SIRT1 in visceral fat tissue. Methods: The metabolic disorder model of spontaneously hypertensive rats was induced by high-fat diet. 17-week-old male spontaneously hypertensive rats (SHR) were selected and divided into two groups: high-fat diet group (n = 12) and normal diet group (n = 5). The normal diet group was given the basic feed and the high-fat diet group was given a high-fat diet. The high-fat diet group was randomly divided into 6 groups (22.5 g/ kg/ day, gavage) and 6 model control groups (with the same volume of distilled water and intragastric administration). Body weight was measured weekly, blood pressure was 2 times, and the amount of drug was changed according to body weight. After 9 weeks of administration, the visceral fat (around the epididymis) of the rat was obtained and weighed, the fat cells were isolated from the part of the visceral fat, the mRNA and the protein were partially extracted, and the part was given 4% paraformaldehyde fixed HE staining.1) The blood pressure and body weight of the SHR rats were monitored regularly by periodically monitoring the blood pressure and body weight of the SHR rats, (2) The expression level of SIRT1 mRNA and protein and caspase-1 protein in visceral fat tissue were determined by RT-PCR and Western Blot method, and the expression level and activity of SIRT1 were assessed. The effect of Qinggan Zishen traditional Chinese medicine (No. 鈪，

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