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缬沙坦干预瞬时受体电位通道C亚族3亚型的表达对小鼠心肌纤维化的影响

Effects of valsartan on myocardial fibrosis in mice by interfering transient receptor potential canonicl 3 expression
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摘要 目的探讨瞬时受体电位通道C亚族3亚型(TRPC3)在心肌纤维化中所起作用,以及缬沙坦干预TRPC3的表达对心肌纤维化的影响。方法取50只昆明种小鼠,随机分为五组,分别为空白组,对照组,低、中、高剂量给药组,每组各10只。其中对照组,各给药组小鼠皮下注射异丙肾上腺素制造心肌纤维化模型,空白组小鼠皮下注射相同体积的0.9%氯化钠注射液。从造模第5天开始,低剂量给药组予以缬沙坦10 mg/(kg·d)灌胃,中剂量给药组予以缬沙坦20 mg/(kg·d),高剂量给药组予以缬沙坦30 mg/(kg·d),均连续灌胃20 d;空白组、对照组每天给予相同体积的0.9%氯化钠注射液灌胃,连续灌胃20 d。灌胃处理结束后,记录小鼠心电图,计算心脏质量指数(HWI),RT-PCR测定心肌组织TRPC3mRNA表达,免疫印迹法测心肌组织TRPC3蛋白、Ⅰ、Ⅲ型胶原表达量。结果五组间的HWI、心率(HR)、T波峰点到末端的间期(Tp-e)、Tp-e/校正Q波起点到T波终点间期(Q-Tc),Ⅰ与Ⅲ型胶原纤维相对表达量、TRPC3mRNA与TRPC3蛋白相对表达量比较,差异均有统计学意义(F=5.416、5.780、33.752、38.011、189.692、94.940、6.501、80.009,P <0.05)。与空白组比较,对照组HWI增大(P <0.05),对照组与低剂量给药组HR、Tp-e、Tp-e/Q-Tc升高(P <0.05),对照组、低剂量与中剂量给药组Ⅰ型与Ⅲ型胶原纤维相对表达量、Ⅰ型胶原纤维表达量/Ⅲ型胶原纤维表达量比值升高(P <0.05),对照组、低剂量与中剂量给药组TRPC3蛋白表达升高(P <0.05),对照组、低、中、高剂量给药组TRPC3mRNA表达升高(P <0.05)。与对照组比较,低、中、高剂量给药组HWI减小(P <0.05),中、高剂量给药组HR下降(P <0.05),低、中、高剂量给药组Tp-e、Tp-e/Q-Tc缩短(P <0.05),高剂量给药组Ⅰ型与Ⅲ型胶原纤维相对表达量、Ⅰ型胶原纤维表达量/Ⅲ型胶原纤维表达量比值、TRPC3蛋白与TRPC3mRNA表达水平下降(P <0.05)。与低剂量组比较,高剂量给� Objective To assess the effects of valsartan and possible role of transient receptor potential canonicl 3(TRPC3) in myocardial fibrosis. Methods 50 Kunming mice were randomly divided into blank group, control group, low-dose, medium-dose and high-dose groups, 10 in each group.The control group, low-, medium-, and high-dose groups were subcutaneously injected with isoproterenol(ⅠSO) to build a myocardial fibrosis model, the blank group received saline of the same volume. From the fifth day of modeling, the rats in the experimental groups were given valsartan for 20 days, including 10 mg/(kg·d) in low dose group, 20 mg/(kg·d) in medium dose group, and 30 mg/(kg·d) in high dose group. The blank and control groups were fed by a same volume of normal saline for 20 days. At the end of gavage, electrocardiogram was recorded and heart mass index(HWⅠ) was calculated. The expression of TRPC3 m RNA was measured by RT-PCR, and expression of TRPC3, Ⅰ, Ⅲ collagen in myocardium were measured by Western blot. Results There were significant differences in HWⅠ, heart rate(HR), T wave peak terminal interval(Tp-e), Tp-e/correct the interval from the beginning of Q wave to the end of T wave(Q-Tc), relative expression of collagen Ⅰ and Ⅲ, relative expression of TRPC3 m RNA and TRPC3 protein among the five groups(F=5.416, 5.780, 33.752, 38.011, 189.692, 94.940, 80.009, 6.501;P < 0.05). Compared with the blank group, HWⅠ increased in the control group(P < 0.05), HR, Tp-e and Tp-e/Q-Tc increased in the control group and low dose group(P < 0.05), the relative expression of type Ⅰ and type Ⅲ collagen fibers and the ratio of type Ⅰ collagen fiber expression to type Ⅲ collagen fiber expression increased in the control group, low dose and medium dose groups(P < 0.05),the expression of TRPC3 protein increased in control,low and medium dose groups(P < 0.05), and the expression of TRPC3 m RNA increased in control group, low, medium and high dose groups(P < 0.05). Compared with the control group, HWⅠ decreased in the
作者 罗芳 江力勤 叶俏 Luo Fang;Jiang Liqin;Ye Qiao(Department of Rheumatology and Immunology,the Second Hospital of Jiaxing,Jiaxing 314000,China;Cardiovascular Medicine Department,the Second Hospital of Jiaxing,Jiaxing 314000,China)
出处 《心脑血管病防治》 2021年第6期543-547,共5页 CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT
关键词 缬沙坦 心肌纤维化 瞬时受体电位通道C亚族3亚型 Valsartan Myocardial fibrosis Transient receptor potential canonicl 3
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