Hypoxia-inducible factor-1α attenuates myocardial inflammatory injury in rats induced by coronary microembolization.

To investigated the role of HIF-1α in myocardial inflammatory injury in rats induced by CME and its possible mechanism. Forty SD rats were separated randomly and equally into four groups, i.e. CME+HIF-1α stabilizer dimethyloxalyl glycine (CME+DMOG) group, CME+HIF-1α inhibitor YC-1 (CME+YC-1) group, CME group, and Sham group. HBFP staining, myocardial enzyme assessment, and cardiac ultrasound were used to measure microinfarct, serum c-troponin I (cTnI) level, and Cardiac function. ELISA and western blot were applied for detecting NLRP3 inflammasome pathway and TLR4/MyD88/NF-κB signaling level.Pro-inflammatory factors of IL-18, IL-1ß and TNF-α increased their expression levels after CME, which indicated inflammatory responses in the myocardium. Additionally, in the inflammatory process, NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling were involved. DMOG reverses these effects of CME, whereas YC-1 aggravates these effects. HIF-1α may attenuate myocardial inflammatory injury induced by CME and improve cardiac function, which can perhaps be explained by the fact that TLR4/MyD88/NF-κB signaling pathway activation is inhibited.

Increased interleukin-1α and prostaglandin E2 expression in the spinal cord at 1 day after painful facet joint injury: evidence of early spinal inflammation.

STUDY DESIGN: This study used immunohistochemistry and an enzyme immunoassay to quantify interleukin-1α (IL-1α) and prostaglandin E2 (PGE2) levels in the spinal cord of rats at 1 day after painful cervical facet joint injury. OBJECTIVE: The objective of this study was to determine to what extent spinal inflammation is initiated early after a painful loading-induced injury of the C6-C7 facet joint in a rat model. SUMMARY OF BACKGROUND DATA: A common source of neck pain, the cervical facet joint is susceptible to loading-induced injury, which can lead to persistent pain. IL-1α and PGE2 are associated with joint inflammation and pain, both locally in the joint and centrally in the spinal cord. Joint inflammation has been shown to contribute to pain after facet joint injury. Although spinal neuronal hyperactivity is evident within 1 day of painful facet injury, it is unknown if inflammatory mediators, such as IL-1α and PGE2, are also induced early after painful injury. METHODS: Rats underwent either a painful C6-C7 facet joint distraction or sham procedure. Mechanical sensitivity was assessed, and immunohistochemical and enzyme immunoassay techniques were used to quantify IL-1α and PGE2 expression in the spinal cord at day 1. RESULTS: Both IL-1α and PGE2 were significantly elevated (P≤ 0.04) at day 1 after painful injury. Moreover, although both spinal IL-1α and PGE2 levels were correlated with the withdrawal threshold in response to mechanical stimulation of the forepaw, this correlation was only significant (P = 0.01) for PGE2. CONCLUSION: The increased expression of 2 inflammatory markers in the spinal cord at 1 day after painful joint injury suggests that spinal inflammation may contribute to the initiation of pain after cervical facet joint injury. Further studies will help identify functional roles of both spinal IL-1α and PGE2 in loading-induced joint pain. LEVEL OF EVIDENCE: N/A.

La ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteina de choque 70 / Ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70

Se ha demostrado que la ketamina, una anestésico general, produce una respuesta de choque térmico (HSR) en algunos animales experimentales. Examinamos si la ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteína de choque 70. Un total de 124 ratas Wistar machos se dividieron aleatoriamente en 3 grupos: un grupo de control (grupo C, n = 20), un grupo quemado (grupo B, n = 52) y un grupo quemado + ketamina (grupo K, n = 52). Las ratas de los grupos B y K presentaban quemaduras de espesor completo en el 30% del total de su superficie corporal. Las ratas del grupo K se trataron con ketamina (40mg/kg, i.m.) a los 15min después de la lesión y las del grupo B se inyectaron con igual volumen de solución salina. Luego de practicar la eutanasia a las ratas, se examinó la expresión de HSP70 en muestras del miocardio y del cerebro con análisis Western blot. En las ratas que no se sacrificaron se evaluó el estado de supervivencia. Luego de 10 días, la tasa de supervivencia en las ratas del grupo K era superior a las del grupo B (70% versus 30%). Los análisis Western blot mostraron que la expresión de proteína HSP70 en el miocardio en respuesta a la administración de ketamina es más fuerte que en respuesta a la administración de solución salina a las 3 h (158% versus 65%) y a las 6h (165% versus 68%). En comparación con el grupo B, la ketamina aumentó marcadamente el nivel de expresión de la proteína HSP70 en tejido cerebral a las 3h y a las 6 h (79% versus 51% a las 3 h; 123% versus 98% a las 6 h). Concluimos que el tratamiento con ketamina mejora la supervivencia en lesión por quemadura severa, mediante la expresión de la proteína de choque 70 en los tejidos del miocardio y del cerebro.

Ketamine, a general anesthetic, has been shown to elicit the heat-shock response (HSR) in some of the animal models. We examined whether ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70. 124 male Wistar rats were randomly divided into three groups: a control group (group C, n = 20), burned group (group B, n = 52), and burned + ketamine group (group K, n = 52). The rats in groups B and K had full-thickness burns of 30% of their total body surface. The rats in group K were treated with ketamine (40 mg/kg, i.m.) 15 min after injury, and those in group B were injected with saline at the same volume. After the rats were euthanized, HSP70 expression in myocardium and brain samples was examined by Western blot analysis. Survival status was evaluated for the rats not euthanized. After 10 days, survival rate of rats in group K was higher than that of group B (70% versus 30%). Western blot analyses revealed that HSP70 protein expression in myocardium in response to ketamine administration is stronger than that in response to saline administration at 3 h (158% versus 65%) and 6 h (165% versus 68%). Compared with that in group B, ketamine strongly increased HSP70 protein expression level in cerebral tissue at 3 h and 6 h (79% versus 51%, at 3 h; 123% versus 98%, at 6 h). We concluded that ketamine therapy improves survival in severe burn injury via the expression of heat shock protein 70 in myocardial and cerebral tissues.