Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Life Sci. 2011 Nov 21;89(21-22):795-805. doi: 10.1016/j.lfs.2011.09.010. Epub 2011 Sep 24.
To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on the tissue damage and fibrosis of obstructed ureters, 80 rats were studied.
Atorvastatin, a HMG-CoA reductase inhibitor, was administered to 40 rats at the dose of 20 mg/kg per day 1day before unilateral ligation of ureters and every day thereafter. The other rats served as controls. Eight rats from each group were sacrificed for examination on days 7, 14, 21, 28 and 42 after ligation, respectively. The expressions of transforming growth factor-β1 (TGF-β1), Interleukine-1β (IL-1β), Interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), proliferation cell nuclear antigen (PCNA), and the apoptotic cells in the ureteric smooth muscle were examined.
Hydroureter and fibrosis of the muscle layer became progressively aggravated in the ligated ureters of the atorvastatin-treated group and control group. The severities of hydroureter and muscle layer fibrosis in the ligated ureters of the treated group were significantly less than in the control group. The atorvastatin administration also decreased the expression of TGF-β1, IL-1β, IL-6, TNF-α, PCNA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the treated group.
We concluded that atorvastatin might ameliorate the tissue damage of obstructed ureters, at least partially, via the inhibition on TGF-β1) expression and by diminishing the effects of pro-inflammatory cytokines.
研究 3-羟-3-甲基戊二酰辅酶 A(HMG-CoA)还原酶抑制剂对梗阻性输尿管组织损伤和纤维化的影响,为此研究了 80 只大鼠。
阿托伐他汀(一种 HMG-CoA 还原酶抑制剂),在单侧输尿管结扎前 1 天以 20mg/kg/天的剂量给予 40 只大鼠,并在此后每天给予。其余大鼠作为对照。每组各有 8 只大鼠分别于结扎后第 7、14、21、28 和 42 天处死检查。检测转化生长因子-β1(TGF-β1)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、增殖细胞核抗原(PCNA)和输尿管平滑肌中的凋亡细胞的表达。
阿托伐他汀治疗组和对照组结扎输尿管均出现不同程度的输尿管积水和肌层纤维化,且治疗组结扎输尿管的输尿管积水和肌层纤维化严重程度明显低于对照组。阿托伐他汀治疗还降低了治疗组结扎输尿管平滑肌中 TGF-β1、IL-1β、IL-6、TNF-α、PCNA 和凋亡细胞标记指数的表达。
我们的结论是,阿托伐他汀可能通过抑制 TGF-β1 的表达和减轻促炎细胞因子的作用,改善梗阻性输尿管的组织损伤。