1996 Fiscal Year Annual Research Report

心不全の成因における細胞間情報伝達物質の役割の解明と診断治療への応用

Research Project

Project/Area Number	08407018
Research Institution	Kyoto University
Principal Investigator	篠山重威京都大学, 医学研究科, 教授 (70109007)
Co-Investigator(Kenkyū-buntansha)	木原康樹京都大学, 医学研究科, 助手 (40214853) 村上知行京都大学, 医学研究科, 講師 (00190885) 松森昭京都大学, 医学研究科, 講師 (70135573)
Keywords	心不全 / 心肥大 / ダールラット / 高血圧 / サイトカイン / インターロイキン / TNF / マクロファージ
Research Abstract	【目的】インターロイキン(IL)-1β、腫瘍壊死因子(TNF)-αなどの炎症性サイトカインは、陰性変力作用をもつことにより心筋炎などの炎症性心疾患に伴う心不全への関与が示唆されている。しかし、高血圧などの機械的な負荷による心不全への関与については検討がない。【方法】ダール食塩感受性ラット(DS)、ダール食塩抵抗性ラット(DR)に6週齢より高食塩食を負荷し、食塩負荷前(6週齢)、心肥大期(11週齢)、心不全期(18週齢)にラットを屠殺し以下の検討を行った(1)定量的PCRにより左心室におけるIL-1β、TNF-α、iNOSのmRNAを測定した。(2)免疫組織学的に左心室におけるIL-1β、TNF-α、iNOS陽性細胞及びマクロファージの分布を検討した。心肥大を呈するが心不全へ移行しない高血圧自然発症ラット(SHR-SP)でも同様の検討を行った。【結果】DSは高血圧を呈し、11週齢においてエコー上求心性心肥大を呈したが壁運動は正常であった。その後、左室の拡大と壁運動低下を示し平均18週齢で死亡した。病理組織学的に明らかな心筋壊死は認められなかった。DSの左心室組織中のIL-1βmRNA量は、11週齢でDRの3.9倍、18週齢でDRの6.2倍に増加していた。IL-1βmRNA量は左室重量/体重比、ANPmRNA量と正の相関を示し、エコー上の左室短縮率(%FS)と負の相関を示した。血管内皮細胞、間室のマクロファージにIL-1βの陽性所見を認めた。DSのTNF-αmRNA量はDR左室の一部マクロファージにiNOS陽性所見を認めたRT-PCRでは検出できなかった。SHR-SPのIL-1β、TNF-αmRNA量はWKYと差がなかった。【総括】機械的負荷術による心肥大から心不全への移行に炎症反応が関与していることが示唆された。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Furukawa Y,et al.: "Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model" Circulation. 93. 333-339 (1996)
[Publications] Sasayama S,et al.: "Role of cytokines in the syndrome of heart failure" Int Med. 35. 60-63 (1996)
[Publications] Matsumori A,et al.: "Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction" Biochem Biophys Res Commun. 221. 391-395 (1996)
[Publications] Furukawa Y,et al.: "Immunomodulation by an adenylate cyclase activator,NKH477,in vivo and in vitro" Clin Immunol Immunopathol. 79. 25-35 (1996)
[Publications] Hasegawa K,et al.: "Endothelin-1 and its receptor in hypertrophic cardiomyopathy" Hypertension. 27. 259-264 (1996)
[Publications] Matsumori A,et al.: "Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy" Biochem Biophys Res Common. 222. 678-682 (1996)
[Publications] Matsumori A,et al.: "Antimyosin antibody imaging in clinical myocarditis and cardiomyopathy : principle and application" Int J Cardiol. 54. 183-190 (1996)
[Publications] Matsumori A,et al.: "Inotropic agents differentially inhibit the induction of nitric oxide synthase by endotoxin in cultured macrophages" Life Sci. 59. PL121-PL125 (1996)
[Publications] LiL-X,et al.: "Comparative study of ^<201>TI-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy" Nucl Med. 10. 307-314 (1996)
[Publications] Matsumori A,et al.: "Differential modulation of cytokine production by drugs : Implication for therapy in heart failure" J Mol Cell Cardiol. 28. 2491-2499 (1996)
[Publications] Sasayama S,et al.: "Vesnarinone : A Potential Cytokine Inhibitor" J Cardiac Failure. 2. 251-258 (1996)
[Publications] Shioi T,et al.: "Persistent expression of cytokine in the chronic stage of viral myocarditis in mice" Circulation. 94. 2930-2937 (1996)
[Publications] Matsumori A,et al.: "Newer aspects of pathogenesis of heart failure : Hepatitis C virus infection in myocarditis and cardiomyopathy" J Cardiac Failure. 2(Suppl). S187-S194 (1996)
[Publications] Sasayama S,et al.: "Immunomodulation : A new horizon for medical treatment of heart failure" J Cardiac Failure. 2(Suppl). S287-S294 (1996)
[Publications] Wang W-Z,et al.: "Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis : A possible mechanism through inhibition of nitric oxide production" Circulation. 95. 245-251 (1997)

1996 Fiscal Year Annual Research Report

心不全の成因における細胞間情報伝達物質の役割の解明と診断治療への応用

Principal Investigator

篠山 重威 京都大学, 医学研究科, 教授 (70109007)

Research Products

[Publications] Furukawa Y,et al.: "Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model" Circulation. 93. 333-339 (1996)

[Publications] Sasayama S,et al.: "Role of cytokines in the syndrome of heart failure" Int Med. 35. 60-63 (1996)

[Publications] Matsumori A,et al.: "Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction" Biochem Biophys Res Commun. 221. 391-395 (1996)

[Publications] Furukawa Y,et al.: "Immunomodulation by an adenylate cyclase activator,NKH477,in vivo and in vitro" Clin Immunol Immunopathol. 79. 25-35 (1996)

[Publications] Hasegawa K,et al.: "Endothelin-1 and its receptor in hypertrophic cardiomyopathy" Hypertension. 27. 259-264 (1996)

[Publications] Matsumori A,et al.: "Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy" Biochem Biophys Res Common. 222. 678-682 (1996)

[Publications] Matsumori A,et al.: "Antimyosin antibody imaging in clinical myocarditis and cardiomyopathy : principle and application" Int J Cardiol. 54. 183-190 (1996)

[Publications] Matsumori A,et al.: "Inotropic agents differentially inhibit the induction of nitric oxide synthase by endotoxin in cultured macrophages" Life Sci. 59. PL121-PL125 (1996)

[Publications] LiL-X,et al.: "Comparative study of ^<201>TI-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy" Nucl Med. 10. 307-314 (1996)

[Publications] Matsumori A,et al.: "Differential modulation of cytokine production by drugs : Implication for therapy in heart failure" J Mol Cell Cardiol. 28. 2491-2499 (1996)

[Publications] Sasayama S,et al.: "Vesnarinone : A Potential Cytokine Inhibitor" J Cardiac Failure. 2. 251-258 (1996)

[Publications] Shioi T,et al.: "Persistent expression of cytokine in the chronic stage of viral myocarditis in mice" Circulation. 94. 2930-2937 (1996)

[Publications] Matsumori A,et al.: "Newer aspects of pathogenesis of heart failure : Hepatitis C virus infection in myocarditis and cardiomyopathy" J Cardiac Failure. 2(Suppl). S187-S194 (1996)

[Publications] Sasayama S,et al.: "Immunomodulation : A new horizon for medical treatment of heart failure" J Cardiac Failure. 2(Suppl). S287-S294 (1996)

[Publications] Wang W-Z,et al.: "Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis : A possible mechanism through inhibition of nitric oxide production" Circulation. 95. 245-251 (1997)

篠山重威京都大学, 医学研究科, 教授 (70109007)