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Asian Pac J Trop Med. 2017 Feb;10(2):152-156. doi: 10.1016/j.apjtm.2017.01.003. Epub 2017 Jan 19.

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.

Asian Pacific journal of tropical medicine

Hong-Xia Zhou, Ling-Huan Gao, Ling-Li Meng, Yu-Xin Zhang, Zi-Feng Wei, Dao-Wen Si

Affiliations

  1. Anatomy Department, North China University of Science and Technology, Tangshan 063009, Hebei, China.
  2. Anatomy Department, North China University of Science and Technology, Tangshan 063009, Hebei, China. Electronic address: [email protected].
  3. Jitang College of North China University of Science and Technology, Tangshan 063300, Hebei, China.

PMID: 28237480 DOI: 10.1016/j.apjtm.2017.01.003

Abstract

OBJECTIVE: To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.

METHODS: Sixty SD rat aged 9-12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins.

RESULTS: The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods (P < 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group (P < 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group (P < 0.05).

CONCLUSIONS: Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Keywords: Cerebral hemorrhage; IL-1β; NF-κB; Secondary inflammatory damage; Simvastatin; TLR4

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