Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Abstract

Abstract. The aim of the present study was to determine the effects of ulinastatin (UTI) on brain injury in rats subjected to cardiopulmonary resuscitation (CPR) following asphyxial cardiac arrest (CA) and identify the underlying mechanisms. In total, 100 healthy male Wistar rats were randomly divided into control and treatment groups (n=50). After 4 min of asphyxial CA, all the rats were immediately subjected to CPR. The treatment group animals were administered 15 mg/kg UTI at the onset of resuscitation. The mortality rate in the two groups was recorded at 24 h post-resuscitation. In addition, neurological function was evaluated at 24, 48 and 72 h post-resuscitation using a neurological deficit scale (NDS). Furthermore, the effects of UTI on the Toll-like receptor 4 (TLR4) signaling pathway in brain tissues were determined by assessing TLR4 mRNA expression, nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels at 1, 3, 6, 12, 24, 48 and 72 h post-resuscitation. After 24 h, the mortality rate significantly decreased in the treatment group when compared with the control animals (10 vs. 30%; P<0.05). Additionally, an overt improvement was observed in the NDS score following UTI treatment when compared with the control (P<0.01). Finally, statistically significant decreases in the levels of TLR4 mRNA expression, NF-κB activity and TNF-α and IL-6 were observed in the treatment group at each time point (P<0.01). Therefore, UTI treatment at the onset of CPR significantly inhibits the TLR4 signaling pathway, thereby alleviating the inflammatory responses following resuscitation and improving neurological function.

Ulinastatin Alleviates Neurological Deficiencies Evoked by Transient Cerebral Ischemia via Improving Autophagy, Nrf-2-ARE and Apoptosis Signals in Hippocampus

“…Our recent study further demonstrated that systemic administration of UTI can attenuate amplification of central pro-inflammatory cytokine (PIC) signal pathway in a rat model of cerebral ischemia induced by CA thereby leading to improvement of neurological severity score, brain tissue edema and survival (Jiang et al 2016). Consistent with this result, UTI has been reported to attenuate neuronal nuclear factor (NF)-κB and PICs and further improve neural functions, and inhibition of PICs leads to downregulation of apoptotic signals (Sui et al 2014. These data indicate the beneficial role played by UTI in alleviating cerebral ischemia reperfusion injury.…”

“…This prior study has also shown that stabilizing HIF-1α significantly attenuates increases of Caspase-3 and TUNEL evoked by induction of CA, and thus improves neurological deficits and neuronal edema (Liu et al 2016). In particular, recent studies further suggest that systemic administration of UTI plays a protective role in regulating neurological deficits observed in CA rats via central PIC mechanisms (Sui et al 2014).…”

“…Group 2 (n=18): CA and CPR were performed and 0.5 ml of saline (i.p., every 12 h for 7 days) was given after CA. Group 3 (n=25): CA and CPR were carried out and 20,000 units/kg body weight of UTI (i.p., every 12 h for 7 days) was injected after CA (Sui et al 2014. In additional group, in order to determine effectiveness of UTI 3-methyladenine (3-MA, inhibitor of autophagy; 15 mg/kg/day, i.p.)…”

“…the prior study has suggested that these signals are engaged in transient cerebral ischemia (Cui et al 2016). UTI plays a beneficial role in regulating neurological dysfunctions evoked by cerebral ischemia, and PIC signal and apoptosis mechanisms are likely engaged in the effects (Sui et al 2014. However, the effects of UTI on autophagy and Nrf2 signals are lacking.…”

Effect of combined treatment with linezolid and ulinastatin on respiratory function and serum inflammatory factors in elderly patients with severe pneumonia

“…However, antibiotic treatment is hampered by the nagging problem of drug resistance. Several clinical studies have demonstrated that linezolid, an effective anti-inflammatory and anti-infective drug, is effective in the treatment of severe pneumonia, while ulinastatin restrains proinflammatory factors and mitigates multiple inflammatory responses [9][10][11][12]. In this study, 98 elderly patients with severe pneumonia were chosen as subjects for investigation of the clinical effect of combined use of linezolid and ulinastatin on the patients.…”