만성 복막투석 동물모델에서 복막 내 제1형 수분통로 발현 및 수분이동의 변화 = Altered Expression of Peritoneal Aquaporin-1 and Water Transport during Long-term Peritoneal Dialysis in Rats

다국어 초록 (Multilingual Abstract)

Background:The present work was designed to examine the altered expression of peritoneal AQP-1 and water transport of peritoneal membrane during the long-term peritoneal dialysis with hypertonic glucose solution in rats.
Methods:Eighteen Sprague-Dawley male rats were randomly divided into 2 groups:control rats (n=6) with peritoneal catheter but not dialyzed; rats with peritoneal dialysis (PD) (n=12) were dialyzed with 4.25% glucose dialysate for all exchanges. Before completion of the study, 4 animals in PD group were euthanized owing to nonfunctional catheters or peritonitis, leaving 14 animals for the analysis. Dialysis exchanges were performed 3 times a day with 25 mL/each exchange for 12 weeks. Immunoperoxidase staining was performed using monoclonal anti-AGE antibody and polyclonal anti-AQP-1 antibody. The slides were read by 5 different examiners in a blind fashion. The staining intensity was graded semiquantitively from 0 to 3. The peritoneal membrane function was assessed by performing one-hour peritoneal equilibration tests every 6 week for comparing transport characteristics. Peritoneal membrane transport rate was assessed by D/P of urea nitrogen and D/Do of glucose. Water transport of peritoneal membrane was assessed by D/P of sodium at 12 week.
Results:The expression of peritoneal AQP-1 was increased in rats with PD, compared to control rats. Consistent with this, D/P of sodium in rats with PD was significantly decreased compared to control rats (0.58±0.04 vs 0.86±0.07, p<0.05), indicating high peritoneal water permeability in response to long-term peritoneal dialysis. Moreover, rats with PD were associated with significantly lower D/Do of glucose and higher D/P of urea nitrogen, suggesting high peritoneal membrane transport.
Conclusion:High expression of peritoneal AQP- 1 was associated with an increased peritoneal water permeability in response to long-term peritoneal dialysis with 4.25% glucose for 12 weeks. The underlying mechanisms for the increased AQP-1 expression need to be examined whether it is due to the continuous exposure to the dialysis solution containing high glucose concentration itself or compensatory effects of slowly developed concomitant ultrafiltration failure in chronic peritoneal dialysis.

국문 초록 (Abstract)

목 적:복막 내 존재하는 수분통로의 발현 변화와 이에 따른 기능장애 정도가 장기 복막투석 환자에서 발생하는 한외여과부전에 관여할 것으로 추정되나 이에 대한 보고가 미미한 실정이다. 이에 저자들은 만성 복막투석 동물모델을 이용하여 포도당 투석액에 의한 복막 내 제1형 수분통로의 발현 변화 및 이에 따른 수분이동의 변화를 알아보고자 하였다.
방 법:S-D 수컷 쥐 18마리를 투석하지 않는 대조군 (n=6)과 4.25% 포도당 투석액으로 매일 투석을 시행한 투석군 (n=12)으로 나눴다. 투석액 교환은 25 mL를 매일 3회 3개월간 시행하였다. 복막투과도 비교를 위해 1시간 PET를 1, 6, 12주에 시행하였고, 수분이동의 간접적인 지표인 sodium의 투석액 대 혈액의 농도비를 측정하였다. 복막의 조직학적 분석은 복막을 채취하여 H&E 및 Masson's Trichrome 염색과 AGE 및 AQP-1에 대한 면역조직화학적 염색을 하였다.
결 과:투석군은 대조군에 비해 복막 내 AQP-1 및 AGE의 발현이 중피세포 및 혈관벽에서 현저하게 발현이 증가되어 있었다 (각각 p<0.05). 수분의 이동은 투석군이 대조군에 비해 유의하게 낮았으며 (0.58±0.04 vs 0.86±0.07, p<0.05), 복막투과도는 투석군에서 과투과도 현상을 관찰할 수 있었다.

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