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- 주제어 : inbreds SHR (검색결과 4 건)
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선천성 고혈압 쥐에서 Imatinib Mesylate가 심근 섬유화에 미치는 영향
추은호,임상현,김옥란,장성원,박찬석,김희열,장기육,윤호중,정욱성,승기배,김재형 대한고혈압학회 2011 Clinical Hypertension Vol.17 No.2
Background: Hypertensive myocardial fibrosis promotes abnormalities of cardiac function that may adversely affect the clinical outcome of hypertensive patients. Imatinib mesylate blocks receptor tyrosine kinase and is clinically used to treat leukemia. Platelet-derived growth factor (PDGF) is a downstream target of receptor tyrosine kinases. Cardiac fibroblasts can be activated by PDGF. Thus we evaluated whether imatinib attenuate myocardial fibrosis and prevents diastolic dysfunction in spontaneously hypertensive rats (SHR). Methods: 8 weeks old male SHRs were subjected to treatment with 8 weeks of low dose imatinib (SHR-10; 10 mg/kg), high dose imatinib (SHR-30; 30 mg/kg) or saline (SHR-C; n = 6 in each group). At the age of 16 weeks,all rats underwent hemodynamic studies and Doppler echocardiography, and were sacrificed. Their hearts were extracted for histopathological, immunoblotting and quantitative reverse transcriptase-polymerase chain reaction analyses. Results: While imatinib did not affect blood pressure (BP), it markedly reduced perivascular and interstitial fibrosis in the hearts of SHR. Echocardigram showed that high-dose imatinib significantly reduced left ventricular (LV) wall thickness (septal/posterior wall;SHR-C vs. SHR-30: 18 ± 2/19 ± 2 mm vs. 15 ± 1/14 ± 1 mm; p < 0.05) and improved the parameters of LV diastolic function such as E/A ratio (SHR-C vs. SHR-30: 1.60 ± 0.10 vs. 1.86 ± 0.20; p < 0.05). Imatinib also significantly reduced mRNA expression of collagen III and PDGF β-receptor tyrosine phosphorylation in the hearts of SHR. Conclusions: These results suggest that imatinib, especially high dose, could attenuate myocardial fibrosis and prevent LV diastolic dysfunction in hypertensive rat model by decreased activity of PDGF. Imatinib may provide a potential therapeutic approach for hypertensive heart disease.
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Microarray Analysis in Spontaneously Hypertensive Rat Heart after Losartan Treatment
Sang Won Lee,Yikyung Kim,Kwan Chang Kim,Sejung Sohn,Young Mi Hong 이화여자대학교 의과학연구소 2016 EMJ (Ewha medical journal) Vol.39 No.2
Objectives: Spontaneously hypertensive rats (SHR) are frequently used as rat models of essential hypertension. The mechanism for the development of hypertension is complicated and it is unknown. The renin-angiotensin system (RAS) plays a key role in the control of blood pressure. Microarrays are a powerful tool for studying genetics. The purpose of this study was to investigate changes of gene expression in the heart tissues of SHR after losartan treatment to provide basic data that is useful in the early diagnosis of hypertension and gene treatment. Methods: Rats were divided into three groups: the control (C) group; the hypertension (H) group (SHR), and the losartan (L) group; treated with losartan (10 mg/kg/day) in SHR. Rats were sacrificed at week 5 and microarray analysis was performed. Results: 102 gene expressions including the genes associated with cell proliferation such as Raf1, Uchl1, Btla, Spock1 were increased. The other 139 gene expressions, including the genes related to the regulation of metabolism such as TFIID, Auf1, Bmp, Hub, Taf51 showed decreases in gene expression. A total of 31 genes were differentially expressed in the L group compared to the H group. Of these, 16 genes including the genes associated with macromolecule metabolism such as MGC105766, Ppp1r1a, Rpl3l showed increased expression. The other 15 genes including the genes associated with primary metabolism such as Mcpt4, Ngn3, Tdo, Ak2 Hyal2 showed decreased expressions. Conclusion: According to microarray analysis, there was significant gene expression change in SHR compared with normal rats as well as significant gene expression changes after losartan treatment in SHR.
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진롱후,이훈재,신화연,최보화,윤상민,박창신,이택 대한배뇨장애요실금학회 2011 International Neurourology Journal Vol.15 No.4
Purpose: Overactive bladder is especially common in the elderly, although it is not regarded as a normal part of aging. Thus, we investigated how aging alters the cystometric and detrusor overactivity (DO) parameters and the density of nerve growth factor (NGF) in awake spontaneous hypertensive rats (SHRs) of different ages. Methods: Three age groups of 12- (n=5), 17- (n=6), and 21- (n=6) week-old SHRs (Oriental Bio Inc.) were used. A catheter was implanted into the bladder to record the intravesical pressure (IVP), and a balloon-fitted catheter was positioned in the abdominal cavity to record the intraabdominal pressure (IAP). Of the IVP elevations above 2 cm H2O, DO was defined as a rise in IVP without a simultaneous change in IAP and was counted during the filling phase. We measured the expression of NGF in the bladders by enzyme-linked immunosorbent assay. Results: Both the body and bladder weights significantly increased with age, but the normalized ratio between those was not changed. As for DO, none of the12-week-old rats showed DO, whereas the other groups did. DO increased significantly with age (P=0.0045 by Mantel-Haenszel trend test), although no significant differences were found in DO frequency or pressure between the 17- and 21-week-old age groups. NGF did not show any significant differences among the three groups. Conclusions: Our results showed that SHRs begin to shows DO after a certain age, such as 12 weeks of age, and that the occurrence of DO has a close relationship with aging. However, NGF, which is known to be increased in the bladder wall of patients with overactive bladder, did not show any relationship with aging in this study.
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