[Berberine protects myocardial injury and cardiac dysfunction in a septic rat model].

Objectives: To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it's mechanisms. Methods: SD rats were divided into 3 groups: sepsis group (LPS group), rats were intraperitoneal injected of LPS (10 mg/kg); Berberine intervention group (Ber group), Ber (50 mg/kg, one time per day) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides (LPS); control group (Con group), rats were gavage fed with double distilled water (2 ml/100 g, one time per day) 3 days before intraperitoneal injection of normal saline (1 ml/100 g). LPS group and the Ber group was further divided into 3 subgroups (n=6), and the follow-up experiments were conducted at 6 h, 24 h and 48 h after LPS injection (of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of change of left ventricular pressure (±dp/dtmax) were monitored, the level of cardiac troponin T (cTnT), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was detected by ELISA method, HE staining of myocardial tissues was done to observe myocardial injury; Western blotting method was used to detect the expression of toll-like receptor 4(TLR4) protein in rat myocardial tissue, the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation. The correlation of factors was analyzed with Pearson correlation analysis. Results: Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic function in the heart of LPS-induced rats, as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP, as well as the decreased LVEDP. Compared with the LPS group, the Ber group showed improved myocardial injury, as demonstrated by decreased cTnT at each time point. HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling. These effects were observed early at 6 hours, severe at 24 hours, and become more serious at 48 hours after LPS injection. Further, TLR4 and NF-κB p65 subunits, which were the two key factors of the TLR4/NF-κB signaling, were upregulated in the LPS group and attenuated in the Ber group. Consistently, the expression levels of the downstream cytokines TNF-α and IL-1ß were lower in the Ber group than those in the LPS group (all P<0.05). Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors (all P<0.05). Conclusions: Berberine can improve myocardial injury and cardiac function in sepsis rats, the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB signaling pathway induced by LPS and further reducing the production of TNF-α and IL-1ß.

[Meta-analysis of efficacy and safety of vitamin D supplementation in the treatment of pulmonary tuberculosis].

Objective: To systematically evaluate the efficacy and safety of vitamin D supplementation in the treatment of pulmonary tuberculosis. Methods: Biomedical Database was searched to collect randomized controlled trials (RCT) related to vitamin D supplementation in tuberculosis patients, and the retrieval time was from establishment to November 2019. Two evaluators independently screened the literature and extracted the data. The negative conversion rate of acid-fast-bacilli of sputum smear, the negative conversion rate of mycobacterium tuberculosis culture and the change of serum vitamin D level were the main outcome indicators, and the body mass index was the secondary outcome indicator. The incidence of hypercalcemia and abnormal urinary calcium were used as adverse event indicators and the RevMan 5.2 software was used for meta-analysis. Results: A total of 8 RCT(S) met the inclusion criteria, including 850 patients with tuberculosis. Meta-analysis showed that compared with the control group, negative conversion rate of acid-fast-bacilli of sputum smear and serum vitamin D level increased after 8 weeks of vitamin D supplementation [RR (95%CI) and mean deviation (MD) (95%CI) were 1.06 (1.00, 1.13) and 8.81 (1.81, 15.81), respectively; negative conversion rate of acid-fast-bacilli of sputum smear was not increased at week 4 and 12 [RR (95%CI) were 1.08 (0.97, 1.20) and 1.01 (0.91, 1.12), respectively]; negative conversion rate of mycobacterium tuberculosis culture in sputum was not increased after 4 and 8 weeks [RR (95%CI) were 1.06 (0.91, 1.22) and 1.02 (0.96, 1.08), respectively]; there was no change in body mass index [MD (95%CI):-0.02 (-0.53, 0.50)]; there was increased risk of abnormal urinary calcium [RR (95%CI): 2.45 (1.75, 3.41)], while no increase in risk of hypercalcemia [RR (95%CI): 1.99 (0.96, 4.13)]. Conclusion: Vitamin D supplementation is safe but not effective in the treatment of pulmonary tuberculosis.