ObjectiveBased on cyclic adenosine monophosphate （cAMP）/cAMP-regulated guanine nucleotide exchange factor 1 （Epac1）/Ras-homologous protein 1 （Rap1） signaling pathway to explore the myocardial protective mechanism of Yiqi Huoxue prescription on coronary heart disease （CHD） rats with Qi deficiency and blood stasis syndrome. MethodEighty-eight specific-pathogen-free （SPF） grade male Sprague-Dawley （SD） rats were divided into a sham operation group （n=12） and an experimental group （n=76） according to the random number table. The experimental group underwent a restricted diet and exhaustive swimming combined with left anterior descending （LAD） coronary artery ligation to construct a model of CHD with Qi deficiency and blood stasis syndrome， and electrocardiograms （ECGs） of rats before and after the LAD operation were collected. After the model was successfully established， the rats were randomly divided into model group， Yiqi Huoxue prescription low-dose group （4.28 g·kg^-1）， medium-dose group （8.55 g·kg^-1）， high-dose group （17.1 g·kg^-1）， and Western medicine group （isosorbide mononitrate tablets， 3.6 mg·kg^-1）. Rats were intragastrically administered assigned drugs for 4 weeks consecutively， while the sham operation group and the model group were administered with equal volumes of double distilled water. Twenty-four hours after the final administration， the rats were anesthetized with isoflurane to detect the left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， left ventricular fractional shortening （FS， %）， and ejection fraction （EF， %） by echocardiography. Blood samples were collected from the abdominal aorta for hemorheological measurements， and plasma cAMP levels were determined using enzyme-linked immunosorbent assay （ELISA）. Myocardial tissue was collected for hematoxylin-eosin （HE） staining and Masson staining to observe myocardial pathological damage， and a transmission electron microscope was used to observe ultrastructural changes of myocardial tissue， fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the expressions of myocardial Epac1， Rap1 GTPase activating protein （Rap1GAP） and Rap1 mRNA， and Western blot was used to detect the expressions of myocardial Epac1， Rap1GAP and Rap1 protein. ResultCompared with those in the sham operation group， LVEDD and LVISD of rats in the model group significantly increased （P<0.01）， and the ratios of EF and FS significantly decreased （P<0.01）， indicating symptoms of heart function decline， referred to as "heart Qi deficiency". The viscosity of whole blood and plasma significantly increased （P<0.01）， and the content of cAMP significant increased （P<0.01）. In addition， there was a significant proliferation of collagen fibers in myocardial tissue （P<0.01）， and the ultrastructure of the myocardial tissue was severely damaged， indicating pathological changes consistent with "blood stasis". Real-time PCR results showed that Epac1 and Rap1 mRNA levels in the model group were significantly reduced （P<0.01）， while Rap1GAP mRNA levels were significantly increased （P<0.01）. Western blot analysis showed a significant decrease in Epac1 protein expression （P<0.01） and a significant increase in Rap1GAP protein expression （P<0.05）. Compared with the model group， Yiqi Huoxue prescription improved cardiac function， reduced blood viscosity， lowered plasma cAMP levels， decreased collagen fiber proliferation， and improved myocardial ultrastructure damage in CHD rats with Qi deficiency and blood stasis syndrome. The high-dose group showed the most significant effects. In the high-dose group， Epac1 mRNA and protein expression levels significantly increased （P<0.01）， Rap1 mRNA expression significantly increased （P<0.01）， and Rap1GAP mRNA and Rap1GAP/Rap1 protein expression levels significantly decreased （P<0.05， P<0.01）. ConclusionYiqi Huoxue prescription can improve cardiac function， reduce blood viscosity and plasma cAMP levels， improve myocardial damage， and reduce collagen fiber proliferation in CHD rats with Qi deficiency and blood stasis syndrome. The myocardial protection mechanism may be related to the regulation of the cAMP/Epac1/Rap1 signaling pathway.

Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.