1.Depressive effect on proliferation of vascular smooth muscle cells by tetrandrine in hypertensive rats
Qingping LI ; Zean LU ; Manren RAO
Chinese Journal of Pharmacology and Toxicology 2001;15(2):145-149
To analyse the effect of tetrandrine(Tet) on proliferation of aortic vascular smooth muscle cells ( AVSMC), AVSMC were isolated and cultured from sham-operated rats(Sham), renovascular hypertensive rats〔RHR, 18 weeks after two kidney one clip(2K1C) operation〕, and Tet (50 mg*kg-1*d-1 po for 9 weeks from week 9 after 2K1C operation)treated RHR. The proliferation of AVSMC was detected by MTT method, and the DNA synthesis was evaluated by [3H]-thymidine incorporation. The results showed that ①The ultrastructure of aorta suggested that AVSMC in RHR had transferred from contractile phenotype to synthetic phenotype; ②Compared to Sham, AVSMC from RHR showed a higher proliferative property with a higher cell number and an increased growth rate stimulated by norepinephrine(NE) or angiotensinⅡ(AngⅡ); ③Compared to untreated RHR, AVSMC from Tet treated RHR showed a reduced reactivity to NE- or AngⅡ-stimulated proliferation and growth rate; ④Tet(0.1-10 μmol*L-1) treated in vitro induced a concentration-dependent depression in [3H] thymidine-incorporation stimulated by NE or AngⅡ in AVSMC from either RHR or Sham. This study provides an evidence of increased reactivity to NE or AngⅡ in AVSMC of RHR. Tet inhibits the proliferation and DNA synthesis in AVSMC, depresses the susceptibility of AVSMC to AngⅡ and NE, both contribute to the regression effect on hypertensive vascular remodeling.
2.Effects of tetrandrine on hydroxyproline content and myosin ATPase activity of hypertrophied myocardium in renovascular hypertensive rats
Zean LU ; Qingping LI ; Manren RAO ; Xiyong YU ; Shuguang LIN
Chinese Journal of Pharmacology and Toxicology 2001;15(2):121-124
To study the effects of tetrandrine (Tet) on hypertrophied myocardial hydroxyproline content and myosin ATPase activity, left ventricular hypertrophy(LVH) was induced by renovascular hypertension (two-kidney, one-clip) in rats. Eight weeks after operation Tet 50 mg*kg-1*d-1 and enalapril(Ena) 6 mg*kg-1*d-1 were given by gavage for 8 weeks. The results showed that hydroxyproline content in LVH group was much higher than that of sham-operated one 〔(5.9±0.3) vs (3.6±0.4) mg*g-1 dry weight〕, and was decreased by 28.2% and 39.0% in Tet and Ena groups, respectively. Myosin ATPase activity in LVH group was much lower than that of sham-operated group 〔(0.43±0.09) vs (0.97±0.06) mmol Pi*min-1*g-1 protein, P<0.01〕. In Tet and Ena groups they were 60.5% and 118.6% higher than that of LVH group, respectively. The results suggest that Tet or Ena partially reduce the hydroxyproline content and elevate myosin ATPase activity of hypertrophied myocardium in renovascular hypertensive rats.
3.Research progress in pathogenesis, diagnosis and treatment of traumatic pseudo subarachnoid hemorrhage
Zean LI ; Xiaohong ZHANG ; Li BIE
Chinese Journal of Trauma 2022;38(5):462-466
Pseudo subarachnoid hemorrhage (PSAH) is often secondary to resuscitation or severe traumatic brain injury (TBI) and has a high rate of mortality and disability. It is characterized by symmetrical subarachnoid hyper-density opacities on CT scans and is mainly venous reflux disorder caused by diffuse cerebral swelling for various causes. At present, PSAH is primarily examined by CT with reduction of cranial pressure as the treatment method. However, the CT signs of PASH are similar to subarachnoid hemorrhage caused by ruptured aneurysm, so the positive CT screening rate for PSAH is low. Effect of simple reduction of intracranial pressure on prognosis improvement of PSAH patients is also limited. Clinical understanding of PSAH is still insufficient, resulting in missed or false diagnosis and untimely treatment. The authors review the research progress in pathophysiology, diagnosis and treatment methods of PSAH so as to help clinicians better understand PSAH, make early diagnosis and timely treatment and improve patients′ prognosis.
4.Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid
Ningning ZHENG ; Yu GU ; Ying HONG ; Lili SHENG ; Linlin CHEN ; Feng ZHANG ; Jie HOU ; Weidong ZHANG ; Zean ZHANG ; Wei JIA ; Houkai LI
Journal of Pharmaceutical Analysis 2020;10(6):560-570
Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.