Objective To investigate the effect of BBR on myocardial injury in rats with myocardial fibrosis based on AMPK - mammalian target of rapamycin (mTOR) -UNC-51-like kinase 1 (Ulk1) pathway. Methods Fifty-five healthy male SD rats (n = 11) aged 6 weeks were selected and treated with isoproterenol (concentration 0.5 mg·mL^-1, 5 mg·kg^-1 on the first day, 2.5 mg·kg^-1·d^-1 on the remaining 20 days) by subcutaneous injection for 21 days to induce myocardial fibrosis. After model preparation, the rats were divided into model group, BBR group, BBR+AMPK inhibitor group and metoprolol group, and a blank control group was set up. The rats in each group were given continuous administration for 28 days, and the animals were anesthetized 12 hours after the last administration, and specimens were collected. The activity and mental state of the rats in each group were observed during the experiment. After the experiment, the pathological morphological changes of the myocardium of the rats were observed by HE staining, and the pathological morphology and fibrosis degree of the myocardium of the rats were observed by Masson staining, and the myocardial collagen volume fraction was calculated. The protein expression of AMPK, mTOR, ULK1, p-AMPK, p-mTOR, p-ULK1, Beclin1 and CollagenⅠ in myocardial tissue was detected by Western Blot. Results The blank control group was white, glossy and quick in action; The model group had dry hair color, slow movement, listless spirit and poor activity. Compared with the model group, the symptoms of the experimental group were improved to different degrees. In the blank group, the myocardial fibers were arranged in bundles without typical fibrosis. In the model group, the myocardial fiber arrangement was disordered, a large amount of collagen deposition occurred, and the degree of fibrosis was serious. BBR +AMPK inhibitor group and collagen fiber decreased compared with model group. BBR group and metoprolol group had lower fibrosis degree than BBR+AMPK inhibitor group. In the model group, Beclin1 protein, p-AMPK and p-ULK1 were significantly decreased, while p-mTOR and Collagen Ⅰ were significantly increased. Compared with the model group, Beclin1 protein, p-AMPK and p-ULK1 were increased in BBR group and metoprolol group, while p-mTOR and Collagen I were decreased. Compared with the BBR+AMPK inhibitor group, Beclin1 protein, p-AMPK and p-ULK1 levels were decreased. p-mTOR and Collagen I were elevated. The differences were statistically significant (P<0.05). Conclusion BBR can activate autophagy through AMPK/mTOR/ULK1 pathway to alleviate myocardial damage induced by isoproterenol in rats with myocardial fibrosis, inhibit myocardial fibrosis, and exert myocardial protection function.

Objective To investigate the relationship between PAI-1 gene polymorphism and cerebral venous thrombolysis occlusion. Methods A total of 232 patients with acute ischemic stroke who received RT PA intravenous thrombolysis in our hospital were selected as the research objects. According to whether the patients had reocclusion or hemorrhagic transformation (HT), they were divided into reocclusion rate group (41 cases), HT group (36 cases) and control group (155 cases). The serum PAI-1 level and PAI-1 gene 675 polymorphism were compared between the two groups, and the serum PAI-1 levels of patients with different genotypes were analyzed. Results The serum PAI-I level in the reoxygenation group was significantly higher than that in the control group, while the serum PAI-I level in HT group was significantly lower than that in the control group (P<0.05). Genotype analysis showed that the proportion of patients with 4G/4G genotype in the reocclusion group was significantly higher than that in the control group, while the proportion of patients with 4G/4G in HT group was significantly lower than that in the control group, the difference was statistically significant (P<0.05). Conclusion The level of PAI-1 in patients with acute ischemic stroke after thrombolytic therapy with RT PA is closely related to the level of serum PAI-1, and 4G / 4G at 675 site of PAI-1 gene is an important factor affecting the level of PAI-1, which may be the main reason for the difference of therapeutic effect after thrombolytic therapy with rt-PA.