To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats (RHR), and analyze the association with blood pressure and cold-inducible RNA binding protein (CIRP) mRNA expression in brain tissue.
A completely randomized grouping design, a randomized control animal trial.
Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong.
Male SD rats (n = 460), weighing 80–100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet (Ningbo Jiangnan Instrument Co., Ltd., China).
The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats (n = 400) were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats (n = 60) served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure (SBP) and divided into 3 sub-groups (n = 100 per group): mild hypertensive group (SBP of 160–200 mm Hg), moderate hypertensive group (SBP of 200–220 mm Hg) and severe hypertensive group (SBP > 220 mm Hg). Each group was further divided into two groups (n = 50) under ACE and non-ACE. Normal sham-operated SD rats (n = 60), SBP < 140 mm Hg, were randomly divided into two groups: Sham-operated control group (n = 30) under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22 °C (7:00–19:00) and 12-hour dark of 4 °C(19:00–7:00). The non-ACE group was kept at 22 °C throughout the experiment.
Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction.
Finally 360 rats were involved in the analysis of results. Incidence of stroke: The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent (12-hour) ACE (29.3 % ) as compared with that in non-ACE (17.3 % ) (P < 0.05). Furthermore, the severe hypertensive 2k2c RHR (BP > 220 mm Hg) was found to have much higher incidence of stroke (66 % , 33/50) than the mild (8 % , 4/50) and moderate (18 % ) hypertensive 2k2c RHR. CIRP mRNA in brain tissue: ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR (P < 0.05).
High blood pressure and low expression of CIRP are associated with ACE induced stroke.