Mechanisch induzierte Apoptose und Nekrose in alveolären Typ-II-Zellen - Beeinflussung durch Captopril und L-Arginin

Zusammenfassung

Hintergrund: Alveoläre Typ-II(ATII)-Zellen sind bei Atmung und Beatmung zyklischen Dehnungen ausgesetzt. Verstärkte Dehnung kann zu akuter Lungenschädigung beitragen. Methode: Diese Arbeit untersucht an ATII-Zellen der Ratte den Effekt dreier Dehnungsmuster (definiert durch Frequenz [min^{- 1}] - Oberflächenzunahme [%]: S40 - 13, S60 - 13, S40 - 30) auf Parameter von Apoptose, Nekrose und Zellmembranintegrität im Vergleich zu statischen Kontrollen. Das Dehnungsmuster S40 - 13 simuliert physiologische Atmung, die anderen sollen den Einfluss gesteigerter Frequenz und Amplitude demonstrieren. Ergebnisse: Zwischen der Gruppe S40 - 13 und statischen Kulturen bestanden keine Unterschiede. LDH-Freisetzung und frühapoptotische Zellen waren in den Gruppen S60 - 13 und S40 - 30 im Vergleich zu statischen Kulturen nach 24 h signifikant erhöht (LDH: 0,089 ± 0,014 µg/ml und 0,177 ± 0,050 µg/ml gegenüber 0,050 ± 0,011 µg/ml; frühapoptotische Zellen: 17 ± 3,5 % und 23 ± 3,1 % gegenüber 9,7 ± 1,4 %). Nekrotische Zellen fanden sich nur in der Gruppe S40 - 30 signifikant erhöht (13 ± 2,4 % gegenüber 6,1 ± 0,9 % in statischer Kultur nach 24 h). Captopril und L-Arginin reduzierten das Ausmaß der Apoptose in der Gruppe S40 - 30 nahezu auf das Niveau statischer Kulturen, ohne das Ausmaß an Nekrose und LDH-Freisetzung zu beeinflussen. Schlussfolgerungen: Durch Auslösung von Apoptose und Nekrose an ATII-Zellen kann verstärkte mechanische Dehnung zu akuter Lungenschädigung beitragen. Durch Dehnung mit hoher Amplitude ausgelöste Apoptose kann durch Captopril and L-Arginin verhindert werden.

Abstract

Background: Alveolar type-II(ATII)-cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury. Methods: The influence of three stretching patterns (characterized by frequency [min^{- 1}] - increase in surface area [%]: S40 - 13, S60 - 13, S40 - 30) on parameters of apoptosis, necrosis and membrane integrity in rat ATII cells was compared with that in static cultures. The S40 - 13 stretching pattern simulated normal breathing. The other patterns were chosen to study increased amplitude and frequency. Results: There were no significant differences between the S40 - 13 group and static cultures. LDH release and early apoptotic cells were significantly increased in S60 - 13 and S40 - 30 in comparison with static cultures (LDH: 0.089 ± 0.014 µg/ml and 0.177 ± 0.050 µg/ml versus 0.050 ± 0.011 µg/ml; early apoptosis: 17 ± 3.5 % and 23 ± 3.1 % versus 9.7 ± 1.4 %) at 24 h. Necrosis was significantly increased only in the S40 - 30 group (13 ± 2.4 % versus 6.1 ± 0.9 % in static culture at 24 h). Captopril as well as L-Arginine prevented apoptosis and reduced apoptotic cells to static culture levels in the S40 - 30 group but did not influence necrosis and LDH release. Conclusion: Increased mechanical stretch may contribute to lung injury by induction of apoptosis and necrosis in ATII cells. Apoptosis induced by high amplitude mechanical stretch is prevented by captopril and L-Arginine.

Literatur

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