中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2014年
6期
427-432
,共6页
王晓林%王庸晋%荣书玲%马红彪
王曉林%王庸晉%榮書玲%馬紅彪
왕효림%왕용진%영서령%마홍표
高血压,肺性%心室重塑%细胞因子类%肝细胞生长因子
高血壓,肺性%心室重塑%細胞因子類%肝細胞生長因子
고혈압,폐성%심실중소%세포인자류%간세포생장인자
Pulmonary artery hypertension%Ventricular remodeling%Cytokines%Hepatocyte growth factor
目的 探讨早期肝细胞生长因子(HGF)转基因治疗对肺动脉高压大鼠细胞因子表达及肺血管和右心室重塑的影响.方法 30只SD大鼠按随机数字表法分为3组,每组10只,其中2组腹腔注射野百合碱建立大鼠肺动脉高压模型,作为空病毒转染组(模型组)和HGF基因转染组(HGF组);另外10只腹腔注射生理盐水作为对照组(对照组).HGF组经气管内滴入法转染携带HGF基因的重组腺病毒,模型组气管内滴入空病毒.4周后,组织学检测肺血管及右心室重塑,半定量逆转录-PCR(RT-PCR)检测重塑的肺血管及右心室心肌组织中肿瘤坏死因子(TNF)-α、IL-6、IL-1β和转化生长因子(TGF)-β1的表达量.结果 治疗4周后,模型组大鼠肺血管组织中TNF-α相对表达量为(0.82 ±0.07),IL-6为(1.13 ±0.19),IL-1β为(0.86±0.11),TGF-β1为(1.18 ±0.12),均高于对照组,差异有统计学意义(P＜0.05).HGF组大鼠肺血管中TNF-α为(0.49 ±0.09),IL-6为(0.68±0.09),IL-1β为(0.51 ±0.07),TGF-β1为(0.59 ±0.10);右心室心肌TNF-α为(0.48 ±0.08),IL-6为(0.63 ±0.09),IL-1β为(0.52 ±0.07),TGF-β1为(0.53 ±0.10),均低于模型组,差异有统计学意义(P＜0.05).与对照组相比模型组大鼠肺血管管壁厚度与外径的比值、管壁面积与血管总面积的比值、右心室肥厚指数、右心室心肌细胞横截面积及右心室胶原容积分数均较高(P＜0.05),HGF治疗后上述指标明显改善.结论 早期HGF治疗可改善肺动脉高压大鼠肺血管及右心室重塑,可能与降低肺血管及右心室心肌组织中TNF-α、IL-6、IL-1β和TGF-β1的表达有关.
目的 探討早期肝細胞生長因子(HGF)轉基因治療對肺動脈高壓大鼠細胞因子錶達及肺血管和右心室重塑的影響.方法 30隻SD大鼠按隨機數字錶法分為3組,每組10隻,其中2組腹腔註射野百閤堿建立大鼠肺動脈高壓模型,作為空病毒轉染組(模型組)和HGF基因轉染組(HGF組);另外10隻腹腔註射生理鹽水作為對照組(對照組).HGF組經氣管內滴入法轉染攜帶HGF基因的重組腺病毒,模型組氣管內滴入空病毒.4週後,組織學檢測肺血管及右心室重塑,半定量逆轉錄-PCR(RT-PCR)檢測重塑的肺血管及右心室心肌組織中腫瘤壞死因子(TNF)-α、IL-6、IL-1β和轉化生長因子(TGF)-β1的錶達量.結果 治療4週後,模型組大鼠肺血管組織中TNF-α相對錶達量為(0.82 ±0.07),IL-6為(1.13 ±0.19),IL-1β為(0.86±0.11),TGF-β1為(1.18 ±0.12),均高于對照組,差異有統計學意義(P＜0.05).HGF組大鼠肺血管中TNF-α為(0.49 ±0.09),IL-6為(0.68±0.09),IL-1β為(0.51 ±0.07),TGF-β1為(0.59 ±0.10);右心室心肌TNF-α為(0.48 ±0.08),IL-6為(0.63 ±0.09),IL-1β為(0.52 ±0.07),TGF-β1為(0.53 ±0.10),均低于模型組,差異有統計學意義(P＜0.05).與對照組相比模型組大鼠肺血管管壁厚度與外徑的比值、管壁麵積與血管總麵積的比值、右心室肥厚指數、右心室心肌細胞橫截麵積及右心室膠原容積分數均較高(P＜0.05),HGF治療後上述指標明顯改善.結論 早期HGF治療可改善肺動脈高壓大鼠肺血管及右心室重塑,可能與降低肺血管及右心室心肌組織中TNF-α、IL-6、IL-1β和TGF-β1的錶達有關.
목적 탐토조기간세포생장인자(HGF)전기인치료대폐동맥고압대서세포인자표체급폐혈관화우심실중소적영향.방법 30지SD대서안수궤수자표법분위3조,매조10지,기중2조복강주사야백합감건립대서폐동맥고압모형,작위공병독전염조(모형조)화HGF기인전염조(HGF조);령외10지복강주사생리염수작위대조조(대조조).HGF조경기관내적입법전염휴대HGF기인적중조선병독,모형조기관내적입공병독.4주후,조직학검측폐혈관급우심실중소,반정량역전록-PCR(RT-PCR)검측중소적폐혈관급우심실심기조직중종류배사인자(TNF)-α、IL-6、IL-1β화전화생장인자(TGF)-β1적표체량.결과 치료4주후,모형조대서폐혈관조직중TNF-α상대표체량위(0.82 ±0.07),IL-6위(1.13 ±0.19),IL-1β위(0.86±0.11),TGF-β1위(1.18 ±0.12),균고우대조조,차이유통계학의의(P＜0.05).HGF조대서폐혈관중TNF-α위(0.49 ±0.09),IL-6위(0.68±0.09),IL-1β위(0.51 ±0.07),TGF-β1위(0.59 ±0.10);우심실심기TNF-α위(0.48 ±0.08),IL-6위(0.63 ±0.09),IL-1β위(0.52 ±0.07),TGF-β1위(0.53 ±0.10),균저우모형조,차이유통계학의의(P＜0.05).여대조조상비모형조대서폐혈관관벽후도여외경적비치、관벽면적여혈관총면적적비치、우심실비후지수、우심실심기세포횡절면적급우심실효원용적분수균교고(P＜0.05),HGF치료후상술지표명현개선.결론 조기HGF치료가개선폐동맥고압대서폐혈관급우심실중소,가능여강저폐혈관급우심실심기조직중TNF-α、IL-6、IL-1β화TGF-β1적표체유관.
Objective To investigate the effect of early treatment with hepatocyte growth factor (HGF) on the cytokine expression and pulmonary artery,right ventricular (RV) remodeling in the rat model of pulmonary artery hypertension (PAH).Methods The rat model of PAH was produced by injecting monocrotaline,and the model rats were randomly divided into empty adenovirus transfection group (MCT group,n =10) and HGF gene transfection group(HGF group,n =10).Another group of rats served as the Sham operation group (Sham group n =10).After 4 weeks of HGF gene transfection,the histological sections of the lungs and right ventricular (RV) were stained with hematoxylin-eosin (HE) and the pulmonary artery and RV remodeling were examined.The rat lung sections were also immunostained with antibodies against factor Ⅷ,and the capillary density were calculated.Meanwhile,the mRNA expression of TNF-α,IL-6,IL-1β and TGF-β1 in pulmonary arteries and RV were detected by RT-PCR.Results HGF gene treatment significantly decreased the ratio of vessel wall thickness to pulmonary artery diameter and the ratio of vessel wall area to total area,and increased the capillary density of lung in PAH rats.HGF gene treatment also significantly decreased cross-sectional area of cardiomyocytes and collagen deposited in RV.Moreover,HGF gene treatment significantly decreased the expression of cytokines in pulmonary artery (TNF-α:0.82 ± 0.07 vs 0.49 ± 0.09,IL-6:1.13 ± 0.19 vs 0.68 ± 0.09,IL-1 β:0.86 ± 0.11 vs 0.51 ±0.07,TGF-β1:1.18 ± 0.12 vs 0.59 ± 0.10) and RV (TNF-α:0.79 ± 0.11 vs 0.48 ± 0.08,IL-6:1.03 ±0.11vs0.63±0.09,IL-1β:0.81±0.11 vs 0.52±0.07,TGF-β1:0.94 ±0.12 vs0.53±0.10) in MCT induced PAH rats (P ＜ 0.05).Conclusion Early treatment with HGF improves pulmonary artery and RV remodeling,possibly by decreasing the expression of TNF-α,IL-6,IL-1β and TGF-β1 in pulmonary arteries and RV.
