JP5324557B2 - プロバイオティクス菌株gm−080が心臓炎症と心臓細胞アポトーシスの治療に用いられる組成物及びその用途 - Google Patents
プロバイオティクス菌株gm−080が心臓炎症と心臓細胞アポトーシスの治療に用いられる組成物及びその用途 Download PDFInfo
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Description
動物評価モードの形成:
1.プロバイオティクス菌株GM−080の調製
この実施例では、ラクトバチルス・パラカゼイGM−080(受託番号はCCTCC M 204012)を用いて動物免疫実験を行い、心臓炎症と心臓細胞アポトーシスを治療するプロバイオティクス菌株GM−080の効果を評価した。ラクトバチルス・パラカゼイGM−080(CCTCC M 204012)の菌量は、1gあたり約1×106〜約1×1011コロニー形成単位(colony−forming unit;CFU)(CFU/g)であってもよい。このラクトバチルス・パラカゼイGM−080(CCTCC M 204012)は、凍結乾燥の形にしてもよく、また、その他の成分を含んでもよく、例えばブドウ糖、マルトデキストリン、乳児用調製粉乳、フラクトオリゴ糖、ステアリン酸マグネシウム、ヨーグルト香料、その他の分離しにくい成分、又は前記の任意の組み合わせを含んでもよい。
この実施例では、BALB/cマウス(台湾台北楽斯科生物科技股有限公司)でアレルゲン感作動物実験モデルを作製した。まず、実験マウスを3群の実験群(アレルギー実験群)及び2群の対照群(健康対照群、アレルギー対照群)に分けた。各群はそれぞれ5週齢の雄のマウス7匹(健康対照群)又は8匹(アレルギー対照群、アレルギー実験群)であった。健康対照群とアレルギー対照群のマウスには、口胃挿管(orogastric intubation)の方式を用いて、毎日一回に蒸留水0.2mLを投与した。各アレルギー実験群のマウスには、異なるプロバイオティクス菌株(それぞれ第1の混合菌株、第2の混合菌株、ラクトバチルス・パラカゼイGM−080(CCTCC M 204012))を毎日一回に経口投与し、各匹にそれぞれ約1×106〜1×1011CFU/gを与えた。アレルギー対照群とアレルギー実験群のマウスには、第0日と第14日に、それぞれ腹腔内に2マイクログラム(μg)と6マイクログラム(μg)のオボアルブミン(ovalbumin;OVA)と完全フロイントアジュバント(complete Freund's adjuvant;CFA)を注射し、マウスのアレルギー反応を誘発した。すべてのマウスに対して、28日の処理した後、秤量し、屠殺してから、心臓を取り出して蒸留水で洗浄し、左右心房と左右心室に分けて再び秤量した。
前記マウスの左心室を溶解バッファー(lysis buffer)に入れ、組織100mg/溶解バッファー1mLの割合で、左心室組織を約1分間均質化(homogenize)して、心筋細胞(cardiomyoctyes)内のタンパク質をさらに溶出した。前記溶解バッファーは、20mMのトリスヒドロキシメチルアミノメタン(tris(hydroxymethyl)aminomethane;Tris)溶液、2mMのエチレンジアミン四酢酸(ethylenediaminetetraacetic acid;EDTA)、50mMの2−メルカプトエタノール(2−mercaptoethanol)、10%のグリセリン、プロテアーゼ阻害剤(proteinase inhibitor;Roche)、およびホスファターゼ阻害剤カクテル(phosphatase inhibitor cocktail;sigma)を含み、pHが7.4である。その後、得られたホモジネート(homogenate)を氷上に約10分間置き、約12000×gの遠心力で40分間遠心し、合計二回遠心した。そして、上澄みを回収して−80℃で保存し、その後、評価を行った。
プロバイオティクス菌株GM−080の心臓炎症治療効果の評価:
この実施例において、電気泳動分析とウェスタンブロッティング分析(Western blotting assay)によって、プロバイオティクス菌株GM−080の、心臓炎症と心臓細胞アポトーシスを治療する効果を評価した。以下それぞれ記述する。
JNK 1/2発現量に対する影響の評価:
図2は、本発明の一実施例によるマウス心臓組織のウェスタンブロッティング解析図であり、レーン1−2が健康対照群を表し、レーン3−4がアレルギー対照群を表し、レーン5−6がアレルギー実験群(混合菌株A、即ち第1の混合菌株)を表し、レーン7−8がアレルギー実験群(混合菌株B、即ち第2の混合菌株)を表し、レーン9−10がアレルギー実験群(ラクトバチルス・パラカゼイGM−080(CCTCC M 204012))を表す。図2は、アレルゲン感作マウス心臓組織内の、TLR4(約89kDa)、p−JNK(約54kDaと46kDa)及びJNK 1/2(約54kDaと46kDa)の発現を分析するものである。α−チューブリン(約57kDa)は、内部標準(internal control)とすることにより、前記タンパクの発現量を標準化する。
p−IκB発現量に対する影響の評価:
図5は、本発明の一実施例によるマウス心臓組織のウェスタンブロッティング解析図であり、レーン1−2が健康対照群を表し、レーン3−4がアレルギー対照群を表し、レーン5−6がアレルギー実験群(混合菌株A、即ち第1の混合菌株)を表し、レーン7−8がアレルギー実験群(混合菌株B、即ち第1の混合菌株)を表し、レーン9−10がアレルギー実験群(ラクトバチルス・パラカゼイGM−080(CCTCC M 204012))を表す。図5は、アレルゲン感作のマウス心臓組織内の、p−NFκB(約65kDa)及びp−IκB(約40kDa)の発現を分析するものであり、α−チューブリンは、前記タンパクの発現量を標準化することに用いられる。
発現量に対する影響の評価:
図8は、本発明の一実施例によるマウス心臓組織のウェスタンブロッティング解析図であり、レーン1−2が健康対照群を表し、レーン3−4がアレルギー対照群を表し、レーン5−6がアレルギー実験群(混合菌株A、即ち第1の混合菌株)を表し、レーン7−8がアレルギー実験群(混合菌株B、即ち第1の混合菌株)を表し、レーン9−10がアレルギー実験群(ラクトバチルス・パラカゼイGM−080(CCTCC M 204012))を表す。図8は、アレルゲン感作のマウス心臓組織内の、Bad(約25kDa)及びBax(約23kDa)の発現を分析するものであり、α−チューブリンは、前記タンパクの発現量を標準化することに用いられる。
びカスパーゼ3発現量に対する影響の評価:
図11は、本発明の一実施例によるマウス心臓組織のウェスタンブロッティング解析図であり、レーン1−2が健康対照群を表し、レーン3−4がアレルギー対照群を表し、レーン5−6がアレルギー実験群(混合菌株A、即ち第1の混合菌株)を表し、レーン7−8がアレルギー実験群(混合菌株B、即ち第2の混合菌株)を表し、レーン9−10がアレルギー実験群(ラクトバチルス・パラカゼイGM−080(CCTCC M 204012))を表す。図11は、アレルゲン感作したマウスの心臓組織内の、細胞質のシトクロムC(約11kDa)及び活性化状態のカスパーゼ3(約17kDa)の発現を分析するものであり、α−チューブリンは、前記タンパクの発現量を標準化することに用いられる。
111 糸粒体
103/105 情報伝達路
Claims (4)
- ラクトバチルス・パラカゼイ(Lactobacillus paracasei)GM−080(受託番号CCTCC M 204012)であるプロバイオティクス菌株GM−080を有効成分として含有する医薬用のリン酸化c−Jun N末端キナーゼ(phosphorylated c−Jun N−terminal kinase;p−JNK)、Bcl−2関連死プロモーター(Bcl−2−associated death promoter;Bad)及びBcl−2関連Xタンパク(Bcl−2−associated X protein;Bax)よりなる群から選ばれる1種または2種以上の遺伝子発現抑制剤。
- 前記プロバイオティクス菌株GM−080は、生又は不活化されるものである請求項1に記載の遺伝子発現抑制剤。
- 前記プロバイオティクス菌株GM−080は、その他の混合菌株を更に含むものである請求項1または2に記載の遺伝子発現抑制剤。
- 前記その他の混合菌株は、アシドフィルス菌(Lactobacillus acidophilus)、ラクトバチルス・プランタルム(Lactobacillus plantarum)、ビフィドバクテリウム・ロンガム(Bifidobacterium longum)、発酵乳酸桿菌(Lactobacillus fermentum)、ラクトバチルスブルガリカス(Lactobacillus bulgaricus)、サーモフィルス菌(Streptococcus thermophilus)、ラクトバチルス・クレモリス(Lactobacillus cremoris)、ラクトバチルスパラカゼイサブスピーシーズパラカゼイ(Lactobacillus paracasei subsp.paracasei)、ラクトバチルス・ラムノーサス(Lactobacillus rhamnosus GG)及び前記の任意の組み合わせからなる群より選ばれたものである請求項3に記載の遺伝子発現抑制剤。
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