PMID- 19595129
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20131121
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 89
IP  - 12
DP  - 2009 Mar 31
TI  - [Simvastatin prevents the development of pulmonary hypertension in the rats 
      through reduction of inflammation].
PG  - 855-9
AB  - OBJECTIVE: To investigate the protection of simvastatin on monocrotaline 
      (MCT)-induce pulmonary hypertension (PH) and the mechanism thereof. METHODS: 
      Thirty-two male Sprague-Dawley rats were randomly divided into 4 equal groups: PH 
      group undergoing subcutaneous injection of MCT and then gastric infusion of 
      normal saline (NS) once a day for 21 days, simvastatin control group undergoing 
      subcutaneous injection of NS and then gastric infusion of simvastatin 2 microg/g 
      once a day for 21 days, simvastatin intervention group undergoing subcutaneous 
      injection of MTS and then gastric infusion of simvastatin 2 microg/g once a day 
      for 21 days, and control group undergoing subcutaneous injection and gastric 
      infusion of NS. Three weeks later the mean pulmonary arterial pressure (mPAP) was 
      detected by right heart catheter. Then the rats were killed with their lungs 
      taken out. Arterial wall area/vessel area (W/V), and arterial wall 
      thickness/vessel external diameter (T/D) were calculated. Perivascular 
      inflammation was scored with the subjective scale of 0 (no) to 4 (severe). 
      Pulmonary interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and 
      monocyte chemotactic protein 1 (MCP-1) were tested by ELISA. RESULTS: The mPAP of 
      the simvastatin intervention group was (23 +/- 7) mm Hg, significantly lower than 
      that of the PH group [(34 +/- 9) mm Hg, P < 0.05], but not significantly 
      different from that of the normal control group [(20 +/- 4) mm Hg, P > 0.05]. The 
      W/V and T/D of the simvastatin intervention group were 0.442 +/- 0.061 and 0.325 
      +/- 0.045 respectively, significantly lower than those of the PH group (0.560 +/- 
      0.086 and 0.368 +/- 0.055 respectively, P < 0.01 and P < 0.05). The perivascular 
      inflammation score of the simvastatin intervention group was (2.19 +/- 0.81), 
      significantly lower than that of the PH group (3.40 +/- 0.65, P < 0.05), and the 
      IL-6, TNF-alpha, and MCP-1 levels of the simvastatin intervention group [(264 +/- 
      127), (179 +/- 91), and (697 +/- 211) pg/ml respectively] were all significantly 
      lower than those of the PH group [(765 +/- 179), (447 +/- 86), (4428 +/- 757) 
      pg/ml respectively, all P < 0.01]. CONCLUSION: The protective effects of 
      simvastatin against MCT-induced PH may be associated with the inhibition of the 
      perivascular inflammation and lung IL-6, TNF-alpha, and MCP-1 levels.
FAU - Zhang, Wei-Hua
AU  - Zhang WH
AD  - Department of Respiratory Diseases, Peking Union Medical College Hospital, 
      Chinese Academy of Medical Sciences, Beijing 100730, China.
FAU - Lu, Wei-Xuan
AU  - Lu WX
FAU - Zhang, Yun-Jian
AU  - Zhang YJ
FAU - Ji, Ying-Qun
AU  - Ji YQ
FAU - Liu, Chun-Ping
AU  - Liu CP
FAU - Li, Guo
AU  - Li G
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 73077K8HYV (Monocrotaline)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Hypertension, Pulmonary/chemically induced/*metabolism/*physiopathology
MH  - Interleukin-6/metabolism
MH  - Male
MH  - Monocrotaline/adverse effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Simvastatin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2009/07/15 09:00
MHDA- 2009/11/18 06:00
CRDT- 2009/07/15 09:00
PHST- 2009/07/15 09:00 [entrez]
PHST- 2009/07/15 09:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2009 Mar 31;89(12):855-9.