ABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. METHODS: Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. RESULTS: The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. CONCLUSION: EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.
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Objective: To observe the effect of imatinib mesylate on pulmonary fibrosis (PF) induced by bleomycin in mice and to explore the related mechanism. Methods: Totally 120 C57BL/6 mice were evenly randomized into control group, model group, dexamethasone group and imatinib group. The pulmonary fibrosis model was established using a single intratracheal infusion of bleomycin; the corresponding drugs were given to mice in each group. Ten mice was sacrificed in each group on day 7, 14, and 21 after operation, respectively. The expression of matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1(TGF-β1) in the lung tissues was semi-quantitatively analyzed by immunohistochemistry method. Results: Immunohistochemistry results showed that the expression of TIMP-1, MMP-1, and TGF-β1 in lung tissues of the dexamethasone group and imatinib group was significantly lower than that in the model group(P<0.01). There was a positive correlation between TGF-β1 and TIMP-1 expression(r=0.243, P=0.004). A negative correlation was found between MMP-1 and TIMP-1 in all the other 3 groups other than in the normal control group(r= -0.291, P<0.0001). Conclusion: Imatinib may downregulate TGF-β1 expression, inhibit TIMP-1 expression, and upregulate MMP-1 expression, maintaining the balance of TIMP-1/MMP-1, subsequently inhibit the development of pulmonary fibrosis, showing a similar effect of dexamethasone.
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Objective To evaluate the relationship between serum tissue inhibitors of metaUoproteinase-1 and children with myocarditis,and provide evidences to support the measurement of serum tissue inhibitors of metallopro- teinase-1. Methods Tissue inhibitors of metalloproteinaee-1 and bioehem indexes of the harvested specimens and e -chocardiogram were measured from children with myocarditis(age: 1～14 years old, n = 9) and healthy young chil- dren(age: 1～14 years old, n = 9). Results Children with myocarditis showed reduced ejection fraction and dilated left ventricular compared with healthy children. Tissue inhibitors of metalloproteinaee-1 in children with myocarditis was significantly reduced compared with healthy children. Aspartie acid transanainase, lactate dehydrogenase,creatine kinase, hydroxybutyrie acid dehydrogenase, MB isoenzyrne of creatine kinase, cardiac troponin Ⅰ , C reactive protein showed no difference between two groups. Conclusion The reduced serum level of tissue inhibitors of metallopro- teinase-1 may show the severity of children with myocarditis and maybe one of the mechanisms of children with di- lated cardiomyopathy following myocarditis.
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Objective To investigate the renoprotective effect of irbesartan on tubulointerstitial fibrosis in rats with adriamycin-induced nephropathy and its possible mechanism. Methods Rats received twice-intravenous injections of adriamycin(ADR) after the right kidney was removed. Those rats were randomly assigned to irbesartan treatment group and nephropathy group. Treatment group received 50 mg? kg-1 ? d-1 irbesartan for 4 weeks. Rats with sham operation served as normal control. Proteinuria and serum creatinine of were measured after 4 weeks. Renal histopathological changes were evaluated as well. Immunohistochemistry was used to examine the protein expression of TGF-?1, MMP-9 and TIMP-1. The mRNA levels of MMP-9 and TIMP-1 were detected by in situ hybridization. Results Proteinuria of treatment group decreased significantly as compared to nephropathy group. TGF-?1, TIMP-1 and MMP-9 were significantly lower than that of nephropathy group in tubulointerstitium and consistently associated with tubular degeneration and interstitial fibrosis progressed. Conclusion Irbesartan has a renoprotective effect on tubulointerstitial fibrosis by modulating the ECM degradation.