ObjectiveTo investigate the effects of epinephrine in intestinal injury caused by lipopolysaccharide (LPS) in rats.MethodsFifty SD rats were randomly divided into five groups ( n =10 pet group ):saline control group received intravenous infusion of 0.9％ saline 2.4 ml/( kg· h) ;LPS group received intravenous injection of LPS 6 mg/kg;small-dose,medium-dose,and large-dose epinephrine treatment group received an intravenous infusion of epinephrine 0.12 μg/(kg· min),0.3 μg/( kg· min),and 0.6 μg/( kg· min)after LPS 6 mg/kg intravenous injection,respectively.Intestinal injury was evaluated by intestinal pathological examination.Blood samples were taken at 0,2 and 6 h after LPS infection,and the levels of serum TNF-α,IL-1β and IL-10 were detected by enzyme-linked immunoadsorbent assay.The pathological changes of intestine were observed at 24 h.ResultsPathological examination showed that LPS caused severe congestion,edema,neutrophil infiltration,hemorrhage and cell necrosis in intestine.Compared with LPS group,large-dose epinephrine ameliorated the damage of intestine.In LPS group,serum levels of TNF-α[ ( 1164 ± 145) ng/L],IL-1β[ (521 ±68) ng/L],IL-10 [ (303 ±20) ng/L] all increased compared with control group (P＜0.05)at 2 h.Compared with LPS group,serum levels of TNF-α[ (576 ± 105) ng/L] were significantly depressed (P＜0.05),whereas IL-10 was elevated at 2 h[ (424 ±29) ng/L] and6 h[ (245 ± 14) ng/L] (P＜0.05)in large-dose epinephrine treatment group.Serum IL- 1β levels were unaffected by large-dose epinephrine treatment.Small-dose and medium-dose epinephrine could not reduce the pathological injury of intestine induced by lipopolysaccharide.Compared with LPS group,levels of serum TNF-α,IL-1β and IL-10 were also unaffected by small-dose and medium-dose epinephrine treatment ( all P＞0.05 ) at any time points.ConclusionEpinephrine reduced the intestine injury caused by LPS by down-regulating pro-inflammatory cytokines production and up-regulate anti-inflammatory cytokines production.

Objective To investigate the effects of epinephrine in sepsis-associated lung injury in rats. Methods Thirty SD rats were randomly divided into three groups(n =10 per group):control group received intravenous 0. 9% saline 2. 4 ml/( kg·h ); LPS group received intravenous LPS ( 6 mg/kg ); epi-nephrine treatment group received an infusion of epinephrine 0. 6μg/( kg·min) after LPS intravenous injec-tion . Blood samples were taken at 2 h and 6 h after LPS injection and the levels of serum tumor necrosis factor ( TNF)-α,interleukin( IL)-6 and IL-10 were detected. The rats were sacrificed at 6 h. The lung tissues and bronchoalveolar lavage fluid( BALF) were collected. Pathological changes of the lung tissues were observed under light microscope. Water content of lung,expression of TNF-α,IL-6 and IL-10 in BALF and in serum were detected. Results (1) The water content of lung in LPS group significantly increased compared with that in control group(85. 24% ± 5. 87% vs. 70. 19% ± 5. 87%) and epinephrine group(78. 00% ± 6. 41%) (P<0. 05). (2)Pathological examination showed that LPS could cause pulmonary capillary hyperemia,ede-ma,inflammatory cells infiltration. Atelectasis and alveolar edema were found in small number of lung tissue. Compared with LPS group, epinephrine ameliorated the lung pathological injury. ( 3 ) Compared with LPS group,serum levels of TNF-α and IL-6 significantly decreased ( P <0. 05 ) , whereas IL-10 increased ( P <0. 05) in epinephrine group. (4)Compared with LPS group,BALF levels of TNF-α[(78 ± 9)ng/L vs. (102 ±16)ng/L]andIL-6[(268±42)ng/Lvs.(347±50)ng/L]significantlydepressed(P<0.05),whereas BALFlevelsofIL-10[(210±23)ng/Lvs.(146±34) ng/L]elevated(P <0.05) inepinephrinegroup. Conclusion Epinephrine could reduce the acute lung injury caused by LPS. Its protective effect may be re-lated to decreasing the levels of TNF-α and IL-6,elevating IL-10 level.

Objective:Glaucoma is a multifactorial optic neuropathy with a high rate of irreversible visual loss,and its pathogenesis is complex and still unclear.Elevated intraocular pressure(IOP)is well recognized as the sole modifiable risk factor for the development of glaucoma in the majority of cases.This study aims to compare 2 different methods of inducing chronic ocular hypertension by circumlimbal suture or by laser burns in degree and lasting time of the IOP,different status of the retina and retinal ganglion cells(RGCs),and changes of the microstructure of neurons. Methods:The chronic ocular hypertension models were induced by 2 different ways.One kind of the models was built by unilateral circumlimbal suture(10/0)implantation(suture group),another kind of model was built by laser burns at trabecular meshwork and episcleral veins(laser group).The untreated contralateral eye served as the control group.Changes in IOP were observed and regularly monitored in the 2 groups of rats.HE staining was applied to observe the retinal and optic nerve pathology.Transmission electron microscope(TEM)was used to observe the mitochondrial morphology.RGCs were specifically labeled with Brn3b antibody and counted.The expression of caspase-3 was detected by Western blotting to clarify the apoptosis of RGCs. Results:Compared with the control group,IOP were significantly increased in the suture group and the laser group(both P<0.05).The suture group induced a 1.5-fold elevation of IOP,and sustained for 8 weeks.The laser group induced a 2-fold elevation of IOP for 12 weeks.Both methods could cause RGCs loss(both P<0.05),which were verified by pathology and immune staining of Brn3b.The expressions of caspase-3 were also increased(both P<0.05).The mitochondrial morphology became more fragment,which changed from long shape to round and small one under TEM in 2 models.For comparison,the pathology changes of retinal structure in suture group were not obviously than those in the laser group. Conclusion:Circumlimbal suture can build an effective model of chronic elevated IOP and induce glaucomatous pathologic changes similar to those in the laser photocoagulation,but the pathologic changes are milder than those in laser photocoagulation.Compare with translimbal laser photocoagulation,equipment and skill demand for circumlimbal suture is less.

AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.