摘要
目的探讨在高脂血症大鼠模型中应用缬沙坦进行干预治疗对血脂的影响,并分析其抗炎分子机制。方法选取30只健康雄性Wistar大鼠,利用随机数字表法进行分组,分别设为A组、B组和C组,每组各10只。A组为对照组,给予常规饮食;B组和C组均为高脂血症模型组,两组均进食高脂饲料达8周,其中C组在第9周开始进行缬沙坦14 mg/(kg·d)药物灌肠处理,而B组则采取生理盐水灌肠。待喂养第8周末,采取三组大鼠内眦静脉血,检测其血脂水平和超敏C反应蛋白(hs-CRP)。待第18周末(缬沙坦干预治疗10周后),利用2%戊巴比妥钠行腹腔麻醉后,采取三组大鼠心室内血液,检测血脂水平、血清炎症因子;并留取主动脉全长用于提取RNA,一部分用于HE染色观察动脉内膜的改变。结果第8周末,B、C两组总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)[B组:(10.18±2.06)、(1.71±0.25)mmol/L;C组:(9.32±2.22)、(1.74±0.39)mmol/L]明显高于A组[(2.07±0.43)、(1.12±0.26)mmol/L],差异均有统计学意义(均P<0.05);第18周末,B、C两组的TC值[11.10±2.54)、(10.02±1.99)mmol/L]明显高于A组[(2.58±0.22)mmol/L],B组血清炎症因子hs-CRP、TNF-α、IL-6、IL-8[(166.11±21.09)mg/L、(1.55±0.18)μg/L、(166.85±54.37)ng/L、(410.22±29.27)ng/L]明显高于A组[(85.31±28.51)mg/L、(0.84±0.25)μg/L、(90.07±30.34)ng/L、(270.82±20.11)ng/L],差异均有统计学意义(均P<0.05)。经缬沙坦干预治疗10周后,C组血清中hs-CRP、TNF-α、IL-6[(98.25±12.77)mg/L、(1.18±0.30)μg/L、(92.26±29.37)ng/L]均低于B组,差异均有统计学意义(均P<0.05),缬沙坦干预治疗18周后,B组hs-CRP mRNA、TNF-αmRNA和IL-6 mRNA[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)]明显高于A组[(1.00±0.04)、(1.01±0.03)、(1.02±0.03)]和C组[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)],差异均有统计学意义(均P<0.05)。结论缬沙坦能够降低高脂血症大鼠模型的血脂水平,抑制促炎因子释放,在抗动脉粥样硬化方面发挥出可观的效果。
Objective To explore the intervention effect on blood lipid of valsartan for the rat model with hyperlipi- demia, and to explore the anti-inflammatory molecular mechanism. Methods 30 healthy male Wistar rats were selected by random number table method and they were divided into group A, B and C, 10 rats in each group. Group A was given routine diet as the control group, group B and C were fed with high fat diet for up to 8 weeks, as hyperlipidemia model group. Group C was treated with Valsartan enema 14 mg/kg per day at the 9 weeks, while group B was taken normal saline enema. At the end of 8 weeks after feed, the blood lipid level and high sensitive C reactive protein （hs- CRP） were detected by angular vein blood. At the end of 18 weeks after feed （Valsartan treatment after 10 weeks）. After intraperitoneal cavity anesthesia with 2% Pentobarbital Sodium, the lipid levels, serum inflammatory factors were detected by ventricular blood, and RNA was extracted by the aorta and part of them was used for HEstaining to observe arterial intimal changes. Results At the end of 8 weeks, TC, LDL-C of group B and C [group B： （10.18±2.06）, （1.71±0.25） mmol/L; group C：（9.32±2.22）, （1.74±0.39） mmol/L] were higher than those of group A [（2.07± 0.43）, （1.12±0.26） mmol/L], the differences were statistically significant （all P 〈 0.05）. At the end of 18 weeks, TC of group B and C [（11.10±2.54）, （10.02±1.99） mmol/L] were higher than that of group A [（2.58±0.22） mmol/L], hs-CRP, TNF-α, IL-6, IL-8 of group B [（166.11±21.09）, （1.55±0.18）, （166.85±54.37）, （410.22±29.27） ng/L] were higher than those of group A [（85.31±28.51） mg/L, （0.84±0.25） Ixg/L, （90.07±30.34） ng/L, （270.82±20.11） ng/L], the differences were statistically significant （all P 〈 0.05）. Treated with Valsartan after 10 weeks, hs-CRP, TNF-α, IL-6 of group C [（98.25±12.77） mg/L, （1.18±0.30） μg/L, （92.26±29.37） ng/L] were lower than those of group B （P 〈 0.05）. At end of 18 weeks, hs-CRP mRNA, TNF-α mRNA and IL-6 mRNA of group B [（2.76±0.40）, （3.21±0.46）,（2.33±0.35）] were higher than group A [（1.00±0.04）, （1.01±0.03）, （1.02±0.03）] and group C [（2.76±0.40）, （3.21±0.46）, （2.33±0.35）], the differences were statistically significant （all P 〈 0.05）. hs-CRP mRNA, TNF-α mRNA, IL-6 mRNA were lower than those of group B （P 〈 0.05）. Conehmion Valsartan can reduce the blood lipid level of the model of hyperlipidemia rats, inhibit proinflammatory eytokine release, which plays a significant effect on anti atherosclerosi.
出处
《中国医药导报》
CAS
2014年第16期20-23,共4页
China Medical Herald
基金
浙江省绍兴市农业与社会发展科技项目
关键词
高脂大鼠
缬沙坦
血脂
炎症因子
效果
High fat rats
Valsartan
Blood lipid
Inflammatory factor
Effect
