The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

Abstract

ObjectiveTo investigate the role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH).MethodsThirty-six adult Sprague Dawley (SD) male rats were randomly divided into sham operation, ICH and zinc protoporphyrin (ZPP) group. Rats (except for the sham operation group) were given 50 μL stereotactic injection of autologous blood from the femoral artery into the caudate nucleus, to establish an ICH model. In addition, rats in the ZPP group were given 10 mg/kg intraperitoneal injection of ZPP. At day 3 postoperative, neurobehavioral changes and brain water content were evaluated, brain tissue HO-1 expression was detected with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), brain tissue apoptosis was evaluated with TUNEL method, Caspase 3, Caspase 8 and Caspase 9 activity were detected with colorimetric method, level of TNF-α, IL-1β, IL-6 and IL-8 were measured with the enzyme-linked immunosorbent assay (ELISA), while Bcl-2, Bax, p-NF-κB p65 and p-IκBα protein expression were detected with Western blot.ResultsICH group compared to sham operation: HO-1 positive rate and mRNA expression were increased, neurological deficit score and cell apoptosis rate were increased, Caspase 3, Caspase 8 and Caspase 9 activity were increased, level of TNF-α, IL-1β, IL-6 and IL-8 were increased, Bcl-2 expression was downregulated, Bax, p-NF-κB p65 and p-IκBα expression were upregulated. The differences were statistically significant (P<0.01). ZPP group compared to ICH: HO-1 positive rate and mRNA expression were decreased, neurological deficit score and cell apoptosis rate were decreased, Caspase 3, Caspase 8, Caspase 9 activity were decreased, level of TNF-α, IL-1β, IL-6 and IL-8 were decreased, Bcl-2 expression was upregulated, Bax, p-NF-κB p65 and p-IκBα expression were downregulated, and the differences were statistically significant (P<0.01).ConclusionHO-1 inhibitor, ZPP does have a protective effect on ICH rats. This might be due to its inhibition to the inflammatory reaction and neuronal cell apoptosis.

6 ′‐O‐Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion‐Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation

“…There is an antioxidant response element in its promoter region, which is regulated by Nrf2 [ 30 ]. HO-1 directly affects the antioxidative balance in the body, and it has anti-inflammatory and antiapoptotic activities as well [ 31 , 32 ]. Moreover, GPF administration not only induced Nrf2 expression but also promoted Nrf2 transfer from the cytoplasm to the nucleus in PC12 cells, in a dose-dependent manner ( Figure 3 ).…”

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

“…HO-1, which is regulated by Nrf2, has been recently considered to be important against ischemic brain injury [39]. It directly affects the antioxidative balance in the body, and it has antiapoptotic activities as well [40]. Importantly, the ability to promote Nrf2/HO-1 protein expression and Nrf2 nuclear translocation of UA was significantly blocked after preadministration of brusatol, suggesting that UA may regulate ARE-related gene expression through promoting Nrf2 activation to play antioxidative effects after FCI/R.…”

Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring

“…Bcl-2 protein family is a key regulator of apoptosis and Bax can promote apoptosis while Bcl-2 can inhibit apoptosis, with ratio changes of Bcl-2/Bax directly reflecting the level of apoptosis [ 40 , 41 ]. When stimulated by upstream apoptosis signal, the initiation factors of caspase-8 and caspase-9 are cleaved and activated by other kinases, and the apoptosis signal is then transmitted to the cascade execution factor caspase-3 to induce apoptosis [ 42 ]. The results in the present work suggested that effects of exposure to PM 2.5 during pregnancy on the development of cerebral cortex in mice offspring could be achieved by up-regulating the expressions of Caspase-3, Caspase-8, and Caspase-9, and down-regulating the expression of Bcl-2.…”