Effects Of S100B Expression During Heart Failure In Rats

Calcium is a universal, intracellular second messenger that plays a regulatory role in process or events such as the conduction and transmission of the nerve impulse, muscle contraction, cell motility, cell growth and differentiation, gene expression, cross-talk between different enzyme systems, apoptosis and necrosis. S100 proteins constitute one of the protein families implicated in these fundamental activities, which called "S100" because of its solubility in a 100% saturated solution with ammonium sulfate. S100B is expressed in cell types that constitute nervous system. S100B can also released from cell lineages and interact in a paracrine or an autocrine manner with trophic or apoptotic. Although we have known that S100B inhibits β -protein kinase C signaling, the exacted molecular mechanisms through which S100B modulates heart failure remain to be defined.Objective To evaluate the value of S100B gene in heart failure. Methods Three group of 30 male Sprague-Dawley rats with initial weights of 231g to 248g were studied for 5 weeks. The abdominal aortas of 20 male SD rats were isolated and ligated so as to establish models of heart failure caused by contraction of abdominal aortas. The abdominal aortas of the rest were isolated but not ligated (Sham-Operation Group, S-Group) . Rats were housed in groups of two per cage inan air-coditioned, light-controlled environment and allowed free access to tap water. After one week, the 20 rats were randomly divided into 2 groups: Operation Group, (O-Group) and Car.-Operation Group (Car-Group) . O-Group (n=10) received no spicific therapy and Car-Group (n=10) was treated with 2mg·kg^-1 per day Carvedilol. After 4 weeks, transthoracic echocardiography was performed with rats anesthetized with 10% Chloral hydrate. LVEDD, LVESD and FS were measured from M-mode tracing at the level of the papillary muscles and recorded as the consensus of blinded observers. After echocardiography, a catheter was inserted through the jugular artery into the left ventricle to record LVSP, LVEDP, ±dp/dt and HR. Then all rats were euthanized, and the heart tissues were rapidly excised, rinsed with PBS. Atria were divided from ventricles, and each ventricle was weighed separately. The left ventricles were then cut two partsat the equator: the upper sections were fixation, the lower sections were stored at -80℃,at 100 mg per tube. LV transverse section (4 μ m thick) was subjected to HE and S100B immune-histochemistry. RNA was isolated from tissues by TRIzol to determine levels of S100BmRNA, SERCA2amRNA, RyR₂mRNA, IP₃mRNA, PLBmRNA, β-actinmRNA. Gene expression was compared with their repectively S-Group. Western blot was performed as decribed presviosly. The procedures followed in this study were in accordance with institutional guidelines for experimental animal reseach. Results1. In O-Group and Car-Group of rats, there was a decrease in FS, +dp/dt, -dp/dt; and an increase in LVEDP compared with S-Group.2. In section of O-Group and Car-Group, we found S100B⁺ cells; and there was no S100B⁺cell in S-Group.3. In O-Group and Car-Group of rats, there was a decrease in RyR₂mRNA and IP₃mRNA; and an increase in S100BmRNA compared with S-Group.4. In O-Group and Car-Group of rats, there was an increase in S100B protein compared with S-Group.5. S100B was correlated with LVEDP, +dp/dt, -dp/dt, FS and RyR₂. The value of r was 0.847, -0.853, -0.689, -0.889 and -0.522.Conclusion S100B maybe regulate calcium homeostasis by inhibiting RyR₂; therole of S100B is negative modulator in heart failure and Carvedilol can improve heartfunction.