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Presence of autoantibodies against β1-adrenoceptor aggravates thekidney injury in rats

ZUO Lin, ZHAO Rui, WANG Li, LV Ding-Chao, SHI Shan-Hui, WANG Ke, LI Xiao, LV Ting-Ting, ZHAORong-Rui, LIU Hui-Rong

Deparment of Physiology, Shanxi Medical University, Taiyuan 030001, China； Clinical Inspection Center, Children Hospital ofShanxi, Taiyuan 030001, China； Department of Pathophysiology, Shanxi Medical University, Taiyuan 030001, China； Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, China

Abstract

Since the autoantibodies against the second extracellular loop of β1-adrenoceptor (β1-AABs) have been found in the sera ofpatients with idiopathic dilated cardiomyopathy (IDCM), the involvement of autoimmune mechanisms in the pathogenesis of manycardiovascular diseases has extensively been investigated. Our previous study found that urinary occult blood and protein excretionwere frequently found in the rats with positive β1-AABs, but the mechanisms are unclear. Therefore, we infused the β1-AABs into thevein periodically in an attempt to investigate whether β1-AABs could induce morphological and functional changes in the kidneys ofadult and aged rats and explore the possible mechanisms. The synthetic peptide according to the sequences of the second extracellularloop of β1-adrenoceptor (β1-AR-ECII) was used to immunize the adult rats to acquire enough β1-AABs for use. Neonatal rat ventricularmyocytes (NRVMs) culture was used to observe the biological effects of β1-AABs on the beating rate. The purified β1-AABs weretransfused into the vein of rats. The sera level of blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), urinary specific gravity,protein excretion, occult blood and urinary glucose were detected at the different time points by biochemistry and urine analyzers.HE and Masson’s trichrome staining were used to detect the changes in kidney structure of passively immunized rats. Enhanced greenfluorescent protein (EGFP) and β1-AR-EGFP plasmids were transfected into the human embryonic kidney 293 (HEK293) cellsin order to observe the changes in cell injury with the treatment of β1-AABs. It was found that the sera level of BUN, CR and UAincreased gradually and the ratio of BUN to CR decreased progressively with the administration of β1-AABs. The increasing ofproteinuria, urinary occult blood and urinary glucose was detected by urine analyzer in β1-AABs group. By HE and Masson’scoloration, lots of mononuclear cell infiltration and collagen fibers deposition could be observed at the 24th week of immunization.After the treatment of β1-AABs, the caspase-3 activity increased significantly in the HEK293 cells transfected with β1-AR-EGFPplasmids, while no significant changes were observed for lactate dehydrogenase (LDH) activity. The results indicate that long-termpresence of β1-AABs can induce the morphological and functional damage of the kidneys in adult and aged rats.

Key words: Autoantibody; beta 1 adrenergic receptor; renal insufficiency; chronic

Received: 2014-01-11　　Accepted: 2014-03-11

Corresponding author: 刘慧荣　　E-mail: liuhr2000@126.com

Citing This Article：

ZUO Lin, ZHAO Rui, WANG Li, LV Ding-Chao, SHI Shan-Hui, WANG Ke, LI Xiao, LV Ting-Ting, ZHAORong-Rui, LIU Hui-Rong. Presence of autoantibodies against β1-adrenoceptor aggravates thekidney injury in rats. Acta Physiol Sin 2014; 66 (2): 175-185 (in Chinese with English abstract).