Dr. Xun Tan. College of Veterinary Medicine, Nanjing Agricultural University Department of Veterinary Medicine, Zhejiang Univerity

Transcription

1 L-rginine inhiiting pulmonry vsculr remodelling is ssocited with promotion of poptosis in pulmonry rterioles smooth muscle cells in roilers Dr. Xun Tn College of Veterinry Medicine, Nnjing Agriculturl University Deprtment of Veterinry Medicine, Zhejing Univerity

2 Introduction Broiler pulmonry hypertension syndrome (PHS), lso known s scites syndrome, is metolic disese tht ffects young, fst-growing roilers, nd is considerle cuse of mortlity (Mxwell nd Roertson, 1998).

3 Introduction The primry etiology of PHS in fst-growing roilers: fst growth cool temperture

4 Introduction Pthogenesis of PHS in fst growing roilers fst growth cool temperture incresed metolic demnd for oxygen incresed crdic output inelstic pulmonry vculture oneset of pulmonry hypertension (PH) pulmonry vsculr remodelling sustined PH right ventriculr hypertrophy nd filure incresed pressure in portl system of liver pulmonry hypertension syndrome (PHS)

5 Introduction The effects of L-rginine on PH L-rginine nitric oxide synthse (NOS) nitric oxide (NO) selectively diltes pulmonry vsculture reduces pulmonry rterioles pressure

6 This study ws designed to test the hypothesis: L-rginine inhiits the pulmonry vsculr remodelling during the pthologicl progression leding to pulmonry hypertension in roilers NO-induced poptosis in smooth muscle cells (SMC) is involved in preventing pulmonry vsculr remodelling.

7 Mterils nd Methods Control group (C) nd during weeks 1 nd 2, respectively, nd therefter the temperture ws mintined t Wter nd feed were provided d liitum, nd the lighting schedule ws 24h of light per dy.

8 Mterils nd Methods Cold temperture group (B) nd during weeks 1 nd 2, respectively, nd then sujected to step down temperture progrmme of 1 to 2 per dy from 28 (d14) to14-12 (d21), nd remined consistent until dy 49.

9 Mterils nd Methods L-rginine tretment group (A) sujected to step down temperture progrmme s descried in group B. Also eginning on dy 14, n dditionl 1.0% L-rgninie (Sigm, USA) ws dded to the sl diets.

10 Mterils nd Methods PHS incidence Mesurement of right/totl ventricle rtio (RV/TV) s n index of pulmonry hypertension Detection of plsm NO concentrtion Morphometric nlysis of pulmonry rterioles Detection of poptosis of smooth muscle cells in pulmonry rterioles

11 Results 1. PHS incidence in different groups PHS incidence (%) Groups Group C Group B Group A Different letters designte significnt differences (P < 0.05) mong group vlues.

12 Results 2. Comprison of right/totl ventricle rtio (RV/TV) etween different groups RV/TV rtio Group C Group B Group A 24d 32d 39d 45d Dy of ge Different letters designte significnt differences (P < 0.05) mong group vlues within single smple intervl. The sme is in the following tles.

13 Results 3. Histologicl lesion of pulmonry rterioles Pulmonry section of ird in group B (100< 100<φ 200) (Verhoeff s stin,400, 400 ) Pulmonry section of ird in group A (100<φ 200) (Verhoeff s stin,400 )

14 Results 3. Histologicl lesion of pulmonry rterioles Pulmonry section of ird in group B (φ 60 µm) (Verhoeff s stin,400, 400 ) Pulmonry section of ird in group A (φ 60 µm) (Verhoeff s stin,400, 400 )

15 Results 4. Morphometric nlysis of pulmonry rterioles mmtpa d 32d 39d 45d Dy of ge Vules of men medi thickness in pulmonry rterioles( mmtpa) in different groups Group C Group B Group A

16 Results 4. Morphometric nlysis of pulmonry rterioles WA/TA rtio Vules of vessel wll re/ vessel totl re (WA/TA) in different groups 24d 32d 39d 45d Dy of ge Group C Group B Group A

17 Results 5. Apoptotic smooth muscle cell (SMC) in pulmonry rterioles Apoptotic SMC (rrow) in pulmonry rteriole ( 60 µm) chrcterized y positive stin with TUNEL system ( 400).

18 Results 6. Percentge of poptotic SMC in pulmonry rterioles in different groups Percentge of poptotic cells d 32d 39d 45d Dy of ge Group C Group B Group A

19 Results 7. Plsm NO concentrtion in different groups Plsm NO concentrtion (µ mol L-1) c Group C Group B Group A 24d 32d 39d 45d Dy of ge Plsm NO concentrtion in different groups

20 Conclusion The present study reveled tht pulmonry vsculr remodelling occurred in roilers with pulmonry hypertension, nd the onset of medil hypertrophy of rterioles with n dimeter up to 60 µm egn t s erly s dy 24 of ge.

21 Conclusion The percentge of poptotic SMC in the hypertrophied pulmonry rterioles did not significntly differ from tht in the controls, indicting tht imlnce etween prolifertion nd poptosis in SMC contriutes to pulmonry vsculr remodelling.

22 Conclusion The pthogenesis of pulmonry vsculr remodelling cold exposure incresed pulmonry rterioles pressure incresesed prolifertion of rterioles SMC imlnce etween poptosis nd prolifertion of rteriole SMC incresed WA/TA rtio incresed mmtpa pulmonry vsculr remodelling

23 Conclusion L-rginine supplementtion incresed the percentges of poptotic SMC nd decresed the cross-sectionl vsculr wll re nd medil lyer thickness of the pulmonry rterioles, in ccordnce with elevted plsm NO level, indicting tht L-rginine/NO inhiiting pulmonry vsculr remodelling might e prtilly ssocited with NO-induced poptosis.

24 Conclusion The effect of L-rgine on pulmonry vsculr remodelling L-rginine incresed endogenous NO production induction of poptosis in rteroile SMC reduced WA/TA rtio reduced mmtpa inhition of pulmnory vsculr remodelling

25 Thnk you!