CAJ | 학술논문

目的研究丹参酮ⅡA磺酸钠对低氧性肺动脉高压大鼠模型白细胞介素6(IL-6)表达的影响.方法将SD大鼠(n=32)按随机数字表法分为常氧对照组(A组)、缺氧模型组(B组)、丹参酮ⅡA磺酸钠低剂量(10 mg·kg- 1·d-1)干预组(C组),丹参酮ⅡA磺酸钠高剂量(30 mg·kg-11·d -1)干预组(D组),每组8只.将A组置于常氧中饲养,而B组、C组和D组大鼠则置于常压低氧舱中,低氧舱内氧浓度控制在(10±1)％.C组和D组从缺氧第1天开始,分别每天腹腔注射10 mg/kg、30 mg/kg的丹参酮ⅡA磺酸钠,A组和R组腹腔注射相同容积的生理盐水.连续饲养21d后,右心测压法检测各组大鼠的右心室收缩压及平均动脉压；苏木精-伊红(HE)染色观察大鼠肺小动脉血管形态及炎性反应的组织学变化；ELISA法检测血清的IL-6含量；实时荧光定量PCR法检测肺组织中IL-6的基因表达.结果低氧明显诱导了大鼠平均动脉压及右心室收缩压的升高,而经过丹参酮ⅡA磺酸钠干预后,这种升高显著降低,A、B、C、D各组大鼠的平均动脉压分别为(12.922±0.442) mm Hg(1 mm Hg=0.133 kPa)、(26.737±2.222) mm Hg、( 19.948± 1.681) mm Hg及(18.547±1.090) mm Hg,右心室收缩压分别为(24.677±1.725)mm H g、(63.675±5.283) mm Hg、(49.250±3.816) mm Hg及(41.839±3.993)mm Hg.丹参酮ⅡA磺酸钠改善了低氧性肺动脉高压大鼠肺小动脉血管形态改变及炎性反应,与B组相比,C、D组的肺小动脉管壁和平滑肌层增厚减轻,管腔狭窄及血管周围仅见少量的淋巴细胞及中性粒细胞浸润,但与A组相比,炎性反应仍明显.低氧诱导后,B组IL-6含量较A组明显升高(P＜0.05),丹参酮ⅡA磺酸钠处理后,C、D两组的IIL-6含量较A、B组均降低(均P＜0.05),且C组IL-6含量高于D组(P＜0.05).低氧明显诱导了肺组织中IL-6 mRNA的表达,丹参酮ⅡA磺酸钠则明显抑制低氧大鼠肺组织中IL-6 mRNA的表达水平,但仍高于常氧对照组,即B组＞C组＞D组＞A组(均P＜0.05).结论丹参酮ⅡA磺酸钠可以有效治疗低氧引起的慢性肺动脉高压,可能与其对IL-6的抑制作用有关. 目的研究丹參酮ⅡA磺痠鈉對低氧性肺動脈高壓大鼠模型白細胞介素6(IL-6)錶達的影響.方法將SD大鼠(n=32)按隨機數字錶法分為常氧對照組(A組)、缺氧模型組(B組)、丹參酮ⅡA磺痠鈉低劑量(10 mg·kg- 1·d-1)榦預組(C組),丹參酮ⅡA磺痠鈉高劑量(30 mg·kg-11·d -1)榦預組(D組),每組8隻.將A組置于常氧中飼養,而B組、C組和D組大鼠則置于常壓低氧艙中,低氧艙內氧濃度控製在(10±1)％.C組和D組從缺氧第1天開始,分彆每天腹腔註射10 mg/kg、30 mg/kg的丹參酮ⅡA磺痠鈉,A組和R組腹腔註射相同容積的生理鹽水.連續飼養21d後,右心測壓法檢測各組大鼠的右心室收縮壓及平均動脈壓；囌木精-伊紅(HE)染色觀察大鼠肺小動脈血管形態及炎性反應的組織學變化；ELISA法檢測血清的IL-6含量；實時熒光定量PCR法檢測肺組織中IL-6的基因錶達.結果低氧明顯誘導瞭大鼠平均動脈壓及右心室收縮壓的升高,而經過丹參酮ⅡA磺痠鈉榦預後,這種升高顯著降低,A、B、C、D各組大鼠的平均動脈壓分彆為(12.922±0.442) mm Hg(1 mm Hg=0.133 kPa)、(26.737±2.222) mm Hg、( 19.948± 1.681) mm Hg及(18.547±1.090) mm Hg,右心室收縮壓分彆為(24.677±1.725)mm H g、(63.675±5.283) mm Hg、(49.250±3.816) mm Hg及(41.839±3.993)mm Hg.丹參酮ⅡA磺痠鈉改善瞭低氧性肺動脈高壓大鼠肺小動脈血管形態改變及炎性反應,與B組相比,C、D組的肺小動脈管壁和平滑肌層增厚減輕,管腔狹窄及血管週圍僅見少量的淋巴細胞及中性粒細胞浸潤,但與A組相比,炎性反應仍明顯.低氧誘導後,B組IL-6含量較A組明顯升高(P＜0.05),丹參酮ⅡA磺痠鈉處理後,C、D兩組的IIL-6含量較A、B組均降低(均P＜0.05),且C組IL-6含量高于D組(P＜0.05).低氧明顯誘導瞭肺組織中IL-6 mRNA的錶達,丹參酮ⅡA磺痠鈉則明顯抑製低氧大鼠肺組織中IL-6 mRNA的錶達水平,但仍高于常氧對照組,即B組＞C組＞D組＞A組(均P＜0.05).結論丹參酮ⅡA磺痠鈉可以有效治療低氧引起的慢性肺動脈高壓,可能與其對IL-6的抑製作用有關.
목적 연구단삼동ⅡA광산납대저양성폐동맥고압대서모형백세포개소6(IL-6)표체적영향.방법 장SD대서(n=32)안수궤수자표법분위상양대조조(A조)、결양모형조(B조)、단삼동ⅡA광산납저제량(10 mg·kg- 1·d-1)간예조(C조),단삼동ⅡA광산납고제량(30 mg·kg-11·d -1)간예조(D조),매조8지.장A조치우상양중사양,이B조、C조화D조대서칙치우상압저양창중,저양창내양농도공제재(10±1)％.C조화D조종결양제1천개시,분별매천복강주사10 mg/kg、30 mg/kg적단삼동ⅡA광산납,A조화R조복강주사상동용적적생리염수.련속사양21d후,우심측압법검측각조대서적우심실수축압급평균동맥압；소목정-이홍(HE)염색관찰대서폐소동맥혈관형태급염성반응적조직학변화；ELISA법검측혈청적IL-6함량；실시형광정량PCR법검측폐조직중IL-6적기인표체.결과 저양명현유도료대서평균동맥압급우심실수축압적승고,이경과단삼동ⅡA광산납간예후,저충승고현저강저,A、B、C、D각조대서적평균동맥압분별위(12.922±0.442) mm Hg(1 mm Hg=0.133 kPa)、(26.737±2.222) mm Hg、( 19.948± 1.681) mm Hg급(18.547±1.090) mm Hg,우심실수축압분별위(24.677±1.725)mm H g、(63.675±5.283) mm Hg、(49.250±3.816) mm Hg급(41.839±3.993)mm Hg.단삼동ⅡA광산납개선료저양성폐동맥고압대서폐소동맥혈관형태개변급염성반응,여B조상비,C、D조적폐소동맥관벽화평활기층증후감경,관강협착급혈관주위부견소량적림파세포급중성립세포침윤,단여A조상비,염성반응잉명현.저양유도후,B조IL-6함량교A조명현승고(P＜0.05),단삼동ⅡA광산납처리후,C、D량조적IIL-6함량교A、B조균강저(균P＜0.05),차C조IL-6함량고우D조(P＜0.05).저양명현유도료폐조직중IL-6 mRNA적표체,단삼동ⅡA광산납칙명현억제저양대서폐조직중IL-6 mRNA적표체수평,단잉고우상양대조조,즉B조＞C조＞D조＞A조(균P＜0.05).결론 단삼동ⅡA광산납가이유효치료저양인기적만성폐동맥고압,가능여기대IL-6적억제작용유관.
Objective To investigate the impact of sodium tanshinone Ⅱ A sulfonate (STS) on interleukin-6(IL-6) expression in rat models with hypoxic pulmonary hypertension (HPH).Methods The SD rats (n=32) were randomized into normoxic control group (group A),hypoxia model group (group B),low dose ( 10 mg· kg-1 · d-1 )of STS intervention group (group C ) and higb dose (30 mg· kg-1· d-1 )of STS group (group D) (n=8 each).The group A was fed in normoxic cabin,while the rats of group B,C and D were put into the atmospheric hypoxjc cabin,with the oxygen concentration of atmospheric hypoxic cabin being(10± 1)％.On one hand,10 mg/kg and 30 mg/kg STS were intraperitoneally infused into group C and group D at 1 d after hypoxia respectively.On other hand,the same dose of saline was intraperitoneally infused into group A and group B.After successive feeding of 21 d,right ventricular systolic pressure (RVSP) and mean arterial pressure (mPAP) were detected in rats of each group by right cardiac manometric method,the vascular morphology and inflammatory response observed by hematoxylin- eosin (HE) staining,IL- 6 component in serum measured by ELISA,and the IL-6 expression detected by real-time fluorescent quantitative PCR.Results The hypoxia significantly induced the increases of RVSP and mPAP.Nevertheless,the increasing levels of RVSP and mPAP were obviously decreased after intervention of STS.The mPAPs were (12.922±0.442) mm Hg( 1 mm Hg=0.133 kPa),(26.737±2.222) mm Hg,( 19.948±1.681 ) mm Hg and(18.547± 1.090) mm Hg in A,B,C,D groups,and RVSPs were (24.677 ± 1.725) mm Hg,(63.675±5.283) mm Hg,(49.250±3.816) mm Hg and (41.839±3.993) mm Hg respectively.STS could improve the vascular morphology and inflammatory response in rats with HPH.Compared with group B,group C and group D had reduced thickening of small arterial wall and smooth muscle layer,narrowing lumen and less lymphocytes and neutrophil infiltration in peripheral vessels.However,the inflammatory response in group C and group D remained obvious as compared with that in goup A.After hypoxia induction,the IL-6 component in group B was significantly elevated as compared with that in group A (P＜0.05).While after intervention of STS,the IL-6 components in group C and group D were lowered as compared with those in group A and group B(all P＜0.05),with IL 6 component in group C higher than that in group D(P＜0.05).Hypoxia significantly induced the expression of IL-6 mRNA in hung tissues,while STS obviously inhibited the expression of IL-6 mRNA.However,the expression levels in these groups were still higher than that in normoxic control group,with group B＞ group C＞ group D＞ group A (all P＜0.05).Conclusion STS is effective in treatment of chronicity HPH caused by hypoxia,which may be correlated with its inhibiting effects on IL-6.