당뇨병-고지혈증 모델동물의 개발

Development of Animal Model for Diabetes and Hyperlipidemia

  • 오승현 (서울대학교 수의과대학 발생유전학실) ;
  • 노경진 (서울대학교 수의과대학 발생유전학실) ;
  • 박인선 (인하대학교 의과대학 해부학교실) ;
  • 민본홍 (고려대학교 의과대학 약리학교실) ;
  • 두호경 (경희대학교 한의과대학) ;
  • 안세영 (경희대학교 한의과대학) ;
  • 김용석 (경희대학교 한의과대학) ;
  • 성제경 (서울대학교 수의과대학 발생유전학실)
  • 발행 : 2004.09.01

초록

Diabetic complication is one of major risk factors leading to vascular disease such as atherosclerosis, stroke, coronary heart disease and etc. Several factors affecting the acceleration of diabetic vascular complication have been known such as hypertension, hyperlipidemia, immune complex and genetic factors. To screen and develop new therapeutics agents for diabetic vascular complication, it is strongly needed to develop animal models for diabetic complications. However in rodents models, diabetic complications is not well developed. Furthermore to assess the possibility of new therapeutics for diabetic vascular complications, diabetic animal models which have the risk factors of diabetic complications is needed. We aim to develop and establish an diabetic animal model which have diabetic complications with hyperlipidemia which is one of risk factors for diabetic complications. We induced insulin -dependent diabetes by intra. venous injection of streptozotocin (35 mg/kg/day) in RICO rats which is a spontaneous animal model for hyperlipidemia. Our models (STZ RICO) showed hyperglycemia, persistent high level of plasma cholesterol and triglyceridemia with severe diabetic renal changes until 28 weeks after induction of diabetes. STZ-RICO rats could be used for the evaluations of newly developed diabetic drugs.

키워드

참고문헌

  1. 김용수 방병기. 우리나라 투석요법의 현황. 대한신장학회지, 1991; 11: 187-199
  2. 대한당뇨병학회, 당뇨병의 역학. '당뇨병학' 대한당뇨병학회저, 고려의학, 서울. 1992, 11-24
  3. 류진숙, 이기업. 연령 및 이환기간에 따른 당뇨병 만성 혈관합병증의 유병율과 연관성, 당뇨병, 1992; 16(2) : 145-150
  4. 성제경, 오양석. 고혈압 모델 동물 (SHR)에서 streptozotocin으로 유발한 인슐린 의존형 당뇨병에 관한 연구. 한국실험동물학회지, 1992; 8(2): 161-174
  5. 이태희와 최영길. 당뇨병성혈관합병증의 역학. 당뇨병성혈관합병증, 서울, 고려의학. 1993: 21-30
  6. Abrass CK and Cohen AH. Accelerated glomerulosclerosis in diabetic rats with immunocomplex injury. Diabetes, 1987; 36: 1246-1253 https://doi.org/10.2337/diabetes.36.11.1246
  7. Brown DM and Andres GA. Kidney complications. Diabetes, 1982; 31(Suppl. 1): 71-81 https://doi.org/10.2337/diab.31.1.S71
  8. Brown D.M, Steffes M.W, Thibert P, Azar. S and Maver SM. Glomerular manifestations of diabetes in the BB rat. Metabolism, 32(7) (Suppl. 1): 1983; 131-135 https://doi.org/10.1016/S0026-0495(83)80026-2
  9. Cardona-Sanclemente LE, Ferezou J and Lutton C. Cholesterol metabolism in the genetically hypercholesterolemic (RICO) rat. II. A study of plasma lipoproteins and effect of dietary cholesterol. Biochim Biophys Acta. 1988; 960(3): 382-389 https://doi.org/10.1016/0005-2760(88)90046-X
  10. Cardona-Sanclemente LE, Sultan F and Griglio S. Characterization and quantification of apolipoprotein E in the genetically hypercholesterolemic rat (RICO). Rev Esp Fisiol. 1996: 52(1): 15-22
  11. Cooper ME and Allen TJ. Accelerated progression of diabetic nephropathy in the spontaneously hypertensive streptozotocin diabetic rat. Clin Exp Pharmacol Physiol, 1986; 13: 655-662 https://doi.org/10.1111/j.1440-1681.1986.tb02394.x
  12. Fantappie S, Maggi FM, Cancellieri M, Bosisio E, Malavasi B and Catapano AL. Effect of bezafibrate on plasma lipid in a strain of genetically hypercholesterolemic RICO rats. Pharmacol Res. 1989; 21(Suppl 1): 109-110
  13. Felgines C, Serougne C, Mathe D, Mazur A and Lutton C. Effect of simvastatin treatment on plasma apolipoproteins and hepatic apolipoprotein mRNA levels in the genetically hypercholesterolemic rat (RICO). Life Sci. 1994; 54(5): 361-367 https://doi.org/10.1016/0024-3205(94)00792-6
  14. Felgines C, Serougne C, Mazur A, Ferezou J, Lutton C and Rayssiguier Y. Hepatic apolipoprotein and LDL rece-ptor gene expression in the genetically hypercholes-terolemic (RICO) rat. Atherosclerosis. 1995; 117(1): 15-24 https://doi.org/10.1016/0021-9150(95)05545-8
  15. Hajri T, Ferezou J, Laruelle C and Lutton C. Crilvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A red-uctase inhibitor, inhibits cholesterol absorption in gene-tically hypercholesterolemic rats. Eur J Pharmacol. 1995; 286(2): 131-136 https://doi.org/10.1016/0014-2999(95)00437-P
  16. Luoma H, Alakuijala P, Korhonen A, Nevalainen T, Kuronen M and Jauhiainen M. Serum lipoprotein levels in genetically hypercholesterolaemic RICO rats: effects of a high-sucrose-cholesterol diet without or with altered magnesium and fluoride content. Scand J Clin Lab Invest. 1995; 55(6): 495-503 https://doi.org/10.3109/00365519509075387
  17. Luoma H, Jauhiainen M, Alakuijala P and Nevalainen T. Seven weeks feeding of magnesium and fluoride modi-fies plasma lipids of hypercholesterolaemic rats in late growth phase. Magnes Res. 1998; 11(4): 271-282
  18. Luoma H, Metsa-Ketela T, Jauhiainen M, Alakuijala P, Korhonen A and Nevalainen T. Effects of dietary fluoride and magnesium supplements on cyclic adeno-sine monophosphate (cAMP), calcium and magnesium levels in aorta of genetically hypercholesterolaemic RICO rats. Scand J Clin Lab Invest. 1997; 57(5): 421- 425 https://doi.org/10.3109/00365519709084590
  19. Lutton C. [The RICO rat (genetically hypercholesteremic): a good model for testing a food substance or a drug specific for a key enzyme of cholesterol metabolism]. Reprod Nutr Dev. 1999; 39(4): 481-495 https://doi.org/10.1051/rnd:19990407
  20. Lutton C. Anatomical heterogeneity of the intestinal mucosa and cholesterol homeostasis. A review of studies with normal and genetically hypercholesterolemic (RICO) Rat. Digestion. 1996; 57(1): 1-10
  21. Lutton C and Champarnaud G. Cholesterol synthesis and high density lipoprotein uptake are regulated inde-pendently in rat small intestinal epithelium. Gut. 1994; 35(3): 343-346
  22. Lutton C, Milliat F, Feurgard C, Mathe D, Aigueperse J and Meslin JC. Regional cholesterol synthesis in the intestinal mucosa of the genetically hypercholestero-laemic RICO rat: kinetic study following whole-body gamma-irradiation. Int J Radiat Biol. 1999; 75(2): 175-181 https://doi.org/10.1080/095530099140627
  23. Lutton C, Ouguerram K, Sauvage M and Magot T. Turnover of [14C] sucrose HDL and uptake by organs in the normal or genetically hypercholesterolemic (RICO) rat using a constant infusion method. Reprod Nutr Dev. 1990; 30(1): 97-101 https://doi.org/10.1051/rnd:19900110
  24. Milliat F, Serougne C, Gripois D and Lutton C. Effects of in-sulin deficiency on lipoproteins and their hepatic receptors in Rico rats. CR Acad Sci III. 1998; 321(12): 999-1006 https://doi.org/10.1016/S0764-4469(99)80055-9
  25. Mortimer BC, Beveridge DJ, Phan CT, Lutton C and Redgrave TG. The diurnal rhythms of cholesterol metabolism and plasma clearance of model chylomi-crons: comparison of normal and genetically hyperchol-esterolemic rats (RICO). Comp Biochem Physiol A Mol Integr Physiol. 1998; 120(4): 671-680 https://doi.org/10.1016/S1095-6433(98)10085-5
  26. Ouguerram K, Magot T and Lutton C. Metabolism of intes-tinal triglyceride-rich lipoproteins in the genetically hypercholesterolemic rat. Atherosclerosis. 1992; 93(3): 201-208 https://doi.org/10.1016/0021-9150(92)90256-G
  27. Ouguerram K, Magot T and Lutton C. Metabolism of plasma lipoproteins in the genetically hypercholes-terolemic rat (RICO). Metabolism. 1996; 45(1): 4-11 https://doi.org/10.1016/S0026-0495(96)90193-6
  28. Ramos OL. Diabetes mellitus and hypertension. 1988; 11 (Supp1.1):I-14-I-18
  29. Riottot M, Olivier P, Huet A, Caboche JJ, Parquet M, Khallou J and Lutton C. Hypolipidemic effects of beta-cyclodextrin in the hamster and in the genetically hyper-cholesterolemic Rico rat. Lipids. 1993; 28(3): 181-188 https://doi.org/10.1007/BF02536637
  30. Somani P, Singh HP, Saini RK and Robinovitch A. Strepto-zotocin-induced diabetes in the spontaneously hyper-tensive rat. Metabolism, 1979; 28: 1075-1077 https://doi.org/10.1016/0026-0495(79)90144-6
  31. $\phi$sterby R, Parving HH, Hommel E, Jorgensen HE and Lokkegaard H. Glomerular structure and function in diabetic nephropathy. Early to advanced stages. Dia-betes, 1990;39: 1057-1062
  32. Sultan F, Cardona-Sanclemente LE, Lagrange D, Lutton C and Griglio S. Lipoprotein lipase and hepatic lipase activities in a hypercholesterolaemic (RICO) strain of rat. Effect of dietary cholesterol. Biochem J. 1990; 1; 266(2): 349-353 https://doi.org/10.1042/bj2660349
  33. Tsi D and Tan BK. Effects of celery extract and 3-N-butylphthalide on lipid levels in genetically hypercho-lesterolaemic (RICO) rats. Clin Exp Pharmacol Physiol. 1996; 23(3): 214-217 https://doi.org/10.1111/j.1440-1681.1996.tb02598.x
  34. Yugarani T, Tan BK and Das NP. The effects of tannic acid on serum and liver lipids of RAIF and RICO rats fed on high fat diet. Comp Biochem Physiol Comp Physiol. 1993; 104(2): 339-343 https://doi.org/10.1016/0300-9629(93)90326-Y