title: [Effects of hypertonic sodium chloride hydroxyethyl starch solution on cerebral vasospasm following subarachnoid hemorrhage and its mechanism].
abstract: OBJECTIVE
  To investigate the protective effect and potential mechanisms of hypertonic sodium chloride hydroxyethyl starch solution (HSH) against the cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH).
  
  
  METHODS
  Twenty-four male Sprague-Dawley (SD) rats were randomly assigned to four groups according to the random number table, with 6 rats in each group. The SAH-CVS model was reproduced by injection of the blood twice through the cisterna magna. Rats in both model and HSH treatment groups received 8 mL/kg normal saline (NS) or HSH treatment everyday via caudal vein. Rats in sham group were injected with 1.5 mL/kg NS into cisterna magna followed by 8 mL/kg NS treatment. Rats in normal group received no treatment. Rats were sacrificed to harvest basilar artery after 7 days. The thickness of vessel wall and lumen area were measured using hematoxylin-eosin (HE) staining. The rate of apoptosis of vascular smooth muscle cell (VSMC) was assessed using flow cytometry. Caspase-3 activity was measured by a fluorometric assay. The expressions of Bax and Bcl-2 were determined by Western Blot. Intracellular reactive oxygen species (ROS) was detected by H2DCFDA.
  
  
  RESULTS
  Compared with normal group, increased thickness of vessel wall (27.72 ± 1.94 μm vs. 18.30 ± 1.10 μm, P<0.05), decreased lumen area (26 115 ± 1 991 μm² vs. 55 080 ± 2 091 μm², P<0.05), and elevation of rate of apoptosis of VSMCs [(35.05 ± 5.54) % vs. (5.93 ± 1.53) %, P<0.05] were found in model group. Compared with model group, decreased thickness of vessel wall (22.55 ± 1.50 μm vs. 27.72 ± 1.94 μm, P<0.05), increase of lumen area (48 115 ± 2 460 μm² vs. 26 115 ± 1 991 μm², P<0.05), and depressed rate of apoptosis of VSMCs [(16.54 ± 5.94) % vs. (35.05 ± 5.54) %, P<0.05] were found in HSH treatment group. Caspase-3 activity, intracellular ROS level, Bax and Bcl-2 expressions in model group were (188.40 ± 19.35)%, (163.50 ± 17.02)%, (208.71 ± 26.04)% and (44.52 ± 9.61) % of those of normal group, and the differences of these parameters between model and normal groups were statistically significant (all P<0.05). Caspase-3 activity, intracellular ROS level, Bax and Bcl-2 expressions in HSH treatment group were (135.05 ± 19.52)%, (119.44 ± 11.50)%, (139.20 ± 18.04)% and (85.35 ± 13.12)% of those of normal group, respectively, and the differences of these parameters between HSH treatment and model groups were statistically significant (all P<0.05). The differences of all measurements between sham and normal groups were not statistically significant.
  
  
  CONCLUSIONS
  The current results demonstrate that HSH attenuates the SAH-induced CVS, alleviates thickness of vessel wall, and increases lumen area via inhibition of VSMCs apoptosis.
authors.affiliation: Department of Critical Care Medicine, Translational Medicine Institute, Chenzhou First People's Hospital, Chenzhou 423000, Hunan, China, Corresponding author: Liu Youtan, Department of Anesthesiology, Hongkong University Shenzhen Hospital, Shenzhen 518053, Guangdong, China, Email: youtanliuhao@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jinhe
authors.initials: J
authors.lastname: Li
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Shi
authors.forename: Xuanying
authors.initials: X
authors.lastname: Li
authors.forename: Youtan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000150:complications; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D006895:Hydroxyethyl Starch Derivatives; D019253:Proto-Oncogene Proteins c-bcl-2; D012462:Saline Solution, Hypertonic; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3