Protective effect of Yiqi-Wenyang-Huoxue-Huatan formula on HHPH rat brain by suppressing excessive endoplasmic reticulum stress
10.3969/j.issn.1000-4718.2017.10.005
- VernacularTitle:益气温阳活血化痰方通过抑制内质网应激对HHPH大鼠脑的保护作用
- Author:
qian Bing XIANG
1
;
Hui GAO
;
jie Xiao JIN
;
yue Yong DAI
;
ying Xiao QIAN
;
wen Xi CHEN
;
tie Wan WANG
Author Information
1. 温州医科大学缺血/再灌注损伤研究所
- Keywords:
Yiqi-Wenyang-Huoxue-Huatan formula;
Hypoxia;
Hypercapnia;
Pulmonary hypertension;
Brain;
Endoplasmic reticulum stress
- From:
Chinese Journal of Pathophysiology
2017;33(10):1759-1767
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether Yiqi-Wenyang-Huoxue-Huatan formula ( YWHHF) attenuats brain injury induced by hypoxia-hypercapnia pulmonary hypertension ( HHPH) in the rats by inhibiting excessive endoplasmic re-ticulum stress response .METHODS:Healthy SPF male SD rats ( n=50 ) were randomly divided into 5 groups: control group, hypoxia-hypercapnia group, low-dose YWHHF group, middle-dose YWHHF group and high-dose YWHHF group. The rats in control group lived in normal environment , while the rats in other 4 groups were raised for 4 weeks in oxygen tank with low oxygen concentration and high CO 2 concentration .YWHHF was perfused in the rats of low-, middle-and high-dose groups at 0.15, 0.3 and 0.6 g/kg daily, respectively.The rats in hypoxia-hypercapnia group were given isomet-ric distilled water.The surgery was performed on the rats after 4 weeks, and the brain and lung tissues were quickly collect-ed to detect brain water content and observe the morphological changes after mean pulmonary artery pressure recording and heart perfusion .The caspase-3 activity and the apoptotic index of the brain cells were determined .The expression of c-Jun N-terminal kinase (JNK), caspase-12, C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) at protein and mRNA levels in brain tissues was detected by Western blot and RT-PCR.RESULTS:Compared with con-trol group, mean pulmonary artery pressure, brain water content, brain apoptotic index, caspase-3 activity, and the protein and mRNA levels of JNK, caspase-12, CHOP and GRP78 in the rest 4 groups were increased , and the brain and lung tis-sues had obvious damage under light microscope .Compared with hypoxia-hypercapnia group , mean pulmonary artery pres-sure, brain water content , brain apoptotic index , caspase-3 activity, and the protein and mRNA expression of JNK , caspase-12, CHOP and GRP78 in low-, middle-and high-dose YWHHF groups were decreased , and the pathological dam-age of the brain and lung tissues was obviously reduced under light microscope .These changes in middle-dose YWHHF group were the most significant .CONCLUSION:YWHHF effectively relieves the brain injury induced by HHPH in rats , which may be associated with inhibiting excessive endoplasmic reticulum stress response .
