摘要
目的观察Intermedin（IMD）对血管紧张素Ⅱ（angiotensionⅡ，AngⅡ）诱导的人肾小球系膜细胞（human mesangial cells，HMCs）增殖的影响及其机制。方法将人肾小球系膜细胞分为5组：A组（对照组）：培养液中不加任何刺激物；B组（AngⅡ组）：10^6moI／LAngⅡ；C组（IMD组）：10^-6moI／LAngⅡ＋10^-7moI／LIMD；D组（PKA抑制剂组）：10^-6moI／LAngⅡ＋10^-6moI／LPKA抑制剂H-89＋10^-7moI／LIMD；E组（氯沙坦组）：10^-6moI／LAngⅡ＋10^-6moI／L氯沙坦。MTF法检测个组HMCs增殖情况；比色法检测羟脯氨酸含量；ELISA试剂盒测量各组细胞上清液中的TGF—β1、cAMP、ERK的表达。结果与AngⅡ组相比，IMD可明显抑制AngⅡ诱导的肾小球系膜细胞的增殖及上清液中转化生长因子（TGF—β1）及羟脯氨酸（Hyp）的表达（P〈0．001），加入PKA抑制剂后IMD上述作用被抑制（P〈0．001）。与对照组相比，AngⅡ组可明显增加cAMP的含量并抑制ERK的表达，在加入IMD后上述作用被抑制（P〈0．001）。结论IMD可明显抑制AngⅡ诱导的肾小球系膜细胞的增殖，其机制可能与其促使cAMP第二信使水平的升高并抑制细胞中的ERK信号通路有关。
Objectives To observe the influence of IMD on the proliferation of HMCs which induced by the Ang H and its mechanism. Methods The HMCs were divided into five groups ： group A （ control group） ： the culture medium without any irritants; group B（ AngⅡ group） ： 10^ -6moI / L of AngⅡ ; group C（ IMD group） ： 10 ^-6moI / L of AngⅡ the ＋ 10^ - 7 mol / L, the IMD ; group D （ PKA group） ： 10 ^-6 moI / L of AngⅡ ＋ 10^ -6 moI / L of PKA inhibitor H - 89 ＋ 10 ^-7 mol / L, the IMD; group E （ Losartan group） ： 10 - 6 moI / LAngⅡ＋ 10^ -6 moI / L losartan. The proliferation of HMCs was measured by MTT. The hydroxyproliue content was measured by colorimetric assay. The expression of TGF - β1 cAMP and ERK in the supernatant were measured by ELISA kit. Results Compared with AngⅡgroup, the IMD can significantly inhibit the proliferation of HMCs which were induced by the AngⅡ and the expression of TGF - β1 and Hyp（ P 〈 0. 001 ） which are in the supernatant, but when added the PKA inhibitor, the above effects were inhibited（ P 〈0.001 ）. Compared with the control group, Ang Ⅱ group significantly increased cAMP content and inhibited the expression of ERK , but after added the IMD, the above effects are inhibited （ P 〈 0. 001 ） . Conclusions IMD can significantly inhibit mesangial cell proliferation induced by AngⅡ and the effects were stronger than the losartan group. The possible mechanism is IMD can promote the level of second messenger（cAMP） and inhibite the signaling pathway of the ERK in the cell.
出处
《国际泌尿系统杂志》
2013年第2期188-191,共4页
International Journal of Urology and Nephrology
基金
山西省科技发展计划项目（20100311096-1）
关键词
肾疾病
细胞增殖
血管紧张素Ⅱ
Kidney Disease
Cell Proliferation
Angiotensin Ⅱ
