[Effects of recombinant human morphogenetic protein-2 on pulmonary artery pressure in acute lung injury caused by endotoxin and mechanism thereof: experiment with rats].
OBJECTIVE
To investigate the effects of recombinant human morphogenetic protein-2 (rhBMP-2) on pulmonary artery pressure in acute lung injury (ALI) caused by endotoxin and mechanism thereof:


METHODS
Sixty Wistar rats were randomly divided into 3 equal groups: control group (Group C), receiving intravenous drip of normal saline (NS) through the femoral vein for 1.5 h; lipopolysaccharide (LPS) control group (Group L), receiving intravenous drip of NS and then LPS; and rhBMP-2 group (Group L(T)), receiving intravenous drip of rhBMP-2 solution and LPS solution successively through the femoral vein,, and then injected with rhBMP-2 through a detaining catheter after 24 and 48 hours respectively. Seventy-two hours later the pulmonary artery pressure (P(pa)) was detected and then all the rats were killed with their left lung taken out. Four hours before the collection of lung tissues 5-bromodeoxyuridine (BrDU) was injected intraperitoneally. Pathological examination was conducted. TUNEL was used to examine the proliferation/apoptosis of the pulmonary artery smooth muscle cells (PASMC). The thickness of pulmonary artery media was measured by microphotography system. RT-PCR and Western blotting were used to detect the mRNA and protein expression of the K(V 1.5) gene. PASMCs were collected to undergo electric physiologic examination of the activity of voltage gated potassium channel (K(V)).


RESULTS
The PPa of Group L was (25.1 +/- 3.5) mmHg, significantly higher than those of Groups C and L(T) [(14.9 +/- 1.9) and (15.3 +/- 1.2) mmHg respectively, both P < 0.01]. The mitotic index of Group L was 3.1% +/- 0.6%, significantly higher than those of Group C and LT (0.4% +/- 0.1% and 0.5% +/- 0.6% respectively, both P < 0.01). The thickness of the pulmonary artery media of Group L was 9.7% +/- 2.8%, significantly greater than those of Groups C and L(T) (5.0% +/- 1.5% and 5.2 +/- 1.7% respectively, both P < 0.01). When the reference voltage was + 70 mV, the current value of the PASMC of Group L was (0.61 +/- 0.03) nA, significantly lower than that of Group L(T) [(0.61 +/- 0.17) nA. P < 0.001], lowering by 74.6%. Western blotting showed that the protein expression and mRNA expression of K(V 1.5) of Group L were both significantly lower than those of Groups C and L(T) (both P < 0.01).


CONCLUSIONS
rhBNP-2 inhibits the proliferation and promotes the apoptosis of the PASMC, thus preventing the pulmonary vascular remodeling and pulmonary artery hypertension with the probable mechanism of activation of the K(V) channel and upregulation of K(V 1.5) gene expression.
Shan
Shi-min
SM
Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Pei
Ling
L
Wang
Jun-ke
JK
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D020287:In Situ Nick-End Labeling; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019485:Bone Morphogenetic Proteins; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins