| Objective To investigate the vascular remodeling in SHR and 2k1C-HR if the form is same. And Examine the expression of MAPK family member ERK1/2, upper stream intermediation kinase MEK1/2 and downstream bottom CPLA2 in the aorta and the kidney small arteries smooth muscle cell (SMC) in two hypertension models, which further clarified the role of ERK1/2 signal pathway on the Generation or Apoptosis of VSMC in two hypertension models, and explored the molecular mechanism of hypertensive vascular smooth muscle cell changes from the cell signal transduction .Methods 5-week-old male Wistar Kyoto (WKY) rat is 36, which were randomly divided into two kidney one clip group (2K1C, 18 rats) and sham normotensive control group (SHAM , 12 rats)and blank control group (CON group, 6 rats), 2K1C group used 0.25mm diameter silver clip part of the left renal artery occlusion. SHAM group, only the left renal artery was isolated, not to other treatments; the control group received no treatment. Post-operative rats in each group were observed after 8 weeks of age , 16 weeks of age and 24 weeks of age . SHR rats did not do special processing, respectively, 8 weeks of age ( SHR8 ,6 rats), 16 weeks of age (SHR16 , 6 rats) and 24 weeks of age (SHR24,6 rats ).All rats were killed rapidly and remove the kidney and thoracic aorta, and half placed in 4% neutral paraformal dehyde solution fixed,paraffin-embedded for HE staining and immunohistochemical staining. The other half rapidly frozen into liquid nitrogen, -80℃refrigerator frozen for Western-blotting detection. Light microscope micrometer was used to measure vascular remodeling changes of the aorta and the kidney small arteries in two hypertension models, Immunohistochemistry, Western blotting techniques methods were used to observe the expression of p-ERK1/2,p-MEK1/2,CPLA2 in SMC of the aorta and the kidney small arteries .Results 1.blood pressure changes: after a week the blood pressure of 2K1C group significantly increased(P<0.01),followed by steady at higher levels (192.58±12.92mmHg) the blood pressure of SHR group heated up from 8-week-old beginning , SHR blood pressure increases as the age increased gradually .After 18 weeks of age, the SHR group blood pressure was significantly higher than that of 2K1C group (P<0.05). 2.the ratio of aorta, renal small artery thickness / lumen diameter in the SHR and 2K1C groups were significantly higher than the same week SHAM group (P<0.01 or P<0.05), the same week-old SHR and 2K1C compared ,8-,16-,24-week-old SHR the ratio of interlobular artery thickness / lumendiameter was significantly higher than that of 2K1C group (P <0.01), SHR glomerular injury all weeks group was significantly higher than the same week 2K1C group (P <0.01). 3.The expression of p-ERK1/2:SHR and 2K1C p-ERK1/2 expression in the aorta and renal small arteries smooth muscle cells were significantly higher than thesame week SHAM. thesame week-old SHR and 2K1C compared , the expression of p-ERK1/2 in the 2K1C16 aorta and 8-,16-,24- week-old group interlobular artery smooth muscle cells was significantly higher than those of SHR group (P<0.05 or P<0.01).4.The expression of p-MEK1/2 : p-MEK1/2 expression in the SHR and 2K1C aorta, renal small arteries smooth muscle cells were significantly higher than that of the age-matched SHAM group. Comparing the same week-old SHR and 2K1C, 16-, 24- week-old 2K1C group aorta, 24- week-old 2K1C group interlobar artery, arcuate artery smooth muscle cells p-MEK1/2 expression was significantly higher than those in SHR group (P<0.05). SHR16 group interlobular arterialsmoothmusclecells p-MEK1/2 expression was significantly higher than those in 2K1C group (P<0.05). 5.The expression of CPLA2 : SHR and 2K1C aorta, renal small arteries smooth muscle cells CPLA2 expression were significantly higher than those in SHAM group (P<0.05 or P<0.01). Comparing the same week-old SHR and 2K1C, 2K1C8, 2K1C16 group interlobar artery, arcuate arteries smooth muscle cells CPLA2 expression were significantly higher than those in SHR group (P <0.05), SHR8, 16,24 interlobular artery CPLA2 weeks group were significantly higher than corresponding 2K1C group (P <0.05 or P <0.01).Conclusion 1.SHR and 2K1C hypertensive model rats have different blood pressure trend. SHR hypertensive rats with the week long-term stability and growth gradually increased, 2K1C not increased gradually with the week-old growth. 2. both SHR and 2K1C hypertensive rats aorta and renal small arteries exist in vascular remodeling .Different models of hypertension is not the same degree of vascular remodeling.3.MEK-ERK1/2- CPLA2 pathway play an important role in SHR and 2K1C hypertensive vascular remodeling in the process, to participate in the reconstruction of the aorta andsmall arteries, smooth muscle cell proliferation /apoptosis imbalance. 4. in SHR and2K1C hypertensive models and different types of the same model,MEK-ERK1/2-CPLA2 pathway play a different role in the vascular remodeling development process... |
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