CAJ | 학술논문

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(LDL-C)[B组：(10.18±2.06)、(1.71±0.25)mmol/L；C组院(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-α mRNA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。目的：探討在高脂血癥大鼠模型中應用纈沙坦進行榦預治療對血脂的影響，併分析其抗炎分子機製。方法選取30隻健康雄性Wistar大鼠，利用隨機數字錶法進行分組，分彆設為A組、B組和C組，每組各10隻。 A組為對照組，給予常規飲食；B組和C組均為高脂血癥模型組，兩組均進食高脂飼料達8週，其中C組在第9週開始進行纈沙坦14 mg/(kg·d)藥物灌腸處理，而B組則採取生理鹽水灌腸。待餵養第8週末，採取三組大鼠內眥靜脈血，檢測其血脂水平和超敏C反應蛋白(hs-CRP)。待第18週末(纈沙坦榦預治療10週後)，利用2%戊巴比妥鈉行腹腔痳醉後，採取三組大鼠心室內血液，檢測血脂水平、血清炎癥因子；併留取主動脈全長用于提取RNA，一部分用于HE染色觀察動脈內膜的改變。結果第8週末，B、C兩組總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)[B組：(10.18±2.06)、(1.71±0.25)mmol/L；C組院(9.32±2.22)、(1.74±0.39)mmol/L]明顯高于A組[(2.07±0.43)、(1.12±0.26)mmol/L]，差異均有統計學意義(均P<0.05)；第18週末，B、C兩組的TC值[11.10±2.54)、(10.02±1.99)mmol/L]明顯高于A組[(2.58±0.22)mmol/L]， B組血清炎癥因子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]明顯高于A組[(85.31±28.51)mg/L、(0.84±0.25)μg/L、(90.07±30.34)ng/L、(270.82±20.11)ng/L]，差異均有統計學意義(均P<0.05)。經纈沙坦榦預治療10週後，C組血清中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組，差異均有統計學意義(均P<0.05)，纈沙坦榦預治療18週後，B組hs-CRP mRNA、TNF-α mRNA和IL-6 mRNA[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)]明顯高于A組[(1.00±0.04)、(1.01±0.03)、(1.02±0.03)]和C組[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)]，差異均有統計學意義(均P<0.05)。結論纈沙坦能夠降低高脂血癥大鼠模型的血脂水平，抑製促炎因子釋放，在抗動脈粥樣硬化方麵髮揮齣可觀的效果。
목적：탐토재고지혈증대서모형중응용힐사탄진행간예치료대혈지적영향，병분석기항염분자궤제。방법선취30지건강웅성Wistar대서，이용수궤수자표법진행분조，분별설위A조、B조화C조，매조각10지。 A조위대조조，급여상규음식；B조화C조균위고지혈증모형조，량조균진식고지사료체8주，기중C조재제9주개시진행힐사탄14 mg/(kg·d)약물관장처리，이B조칙채취생리염수관장。대위양제8주말，채취삼조대서내자정맥혈，검측기혈지수평화초민C반응단백(hs-CRP)。대제18주말(힐사탄간예치료10주후)，이용2%무파비타납행복강마취후，채취삼조대서심실내혈액，검측혈지수평、혈청염증인자；병류취주동맥전장용우제취RNA，일부분용우HE염색관찰동맥내막적개변。결과제8주말，B、C량조총담고순(TC)、저밀도지단백담고순(LDL-C)[B조：(10.18±2.06)、(1.71±0.25)mmol/L；C조원(9.32±2.22)、(1.74±0.39)mmol/L]명현고우A조[(2.07±0.43)、(1.12±0.26)mmol/L]，차이균유통계학의의(균P<0.05)；제18주말，B、C량조적TC치[11.10±2.54)、(10.02±1.99)mmol/L]명현고우A조[(2.58±0.22)mmol/L]， B조혈청염증인자hs-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]명현고우A조[(85.31±28.51)mg/L、(0.84±0.25)μg/L、(90.07±30.34)ng/L、(270.82±20.11)ng/L]，차이균유통계학의의(균P<0.05)。경힐사탄간예치료10주후，C조혈청중hs-CRP、TNF-α、IL-6[(98.25±12.77)mg/L、(1.18±0.30)μg/L、(92.26±29.37)ng/L]균저우B조，차이균유통계학의의(균P<0.05)，힐사탄간예치료18주후，B조hs-CRP mRNA、TNF-α mRNA화IL-6 mRNA[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)]명현고우A조[(1.00±0.04)、(1.01±0.03)、(1.02±0.03)]화C조[(2.76±0.40)、(3.21±0.46)、(2.33±0.35)]，차이균유통계학의의(균P<0.05)。결론힐사탄능구강저고지혈증대서모형적혈지수평，억제촉염인자석방，재항동맥죽양경화방면발휘출가관적효과。
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 giv-en 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). Af-staining 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) μg/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 differ-ences were statistically significant (all P<0.05). hs-CRP mRNA, TNF-αmRNA, IL-6 mRNA were lower than those of group B (P<0.05). Conclusion Valsartan can reduce the blood lipid level of the model of hyperlipidemia rats, inhibit proinflammatory cytokine release, which plays a significant effect on anti atherosclerosi.