姜良铎教授认为外感咳喘存在单纯性的外感咳喘和内伤基础上的外感咳喘两种情况,临床诊治时不可混而同治.外感因素中寒邪居多,单纯性的外感咳喘治宜祛寒宣肺、解痉平喘,方用桂枝加厚朴杏子汤临证加减;内伤基础上的外感咳喘则病情复杂,脏腑相关、内外影响,姜老认为内伤基础上的外感咳喘诊治尤其注重肝肺关系.在外感咳喘的辨证上姜老注重"望咽喉"及判断"有无肺燥".现将其经验总结如下,并附典型病例说明.

目的 评价大黄附子汤治疗成人脓毒症胃肠功能障碍的疗效及安全性.方法 由2名研究人员分别独立通过计算机检索PubMed、Cochrane临床试验数据库、Medline、中国知网(CNKI)、万方数据库、中国生物医学文献数据库(CBM)、维普中文期刊数据库建库至2019年8月公开发表的关于大黄附子汤治疗成人脓毒症急性胃肠功能障碍的随机对照临床试验,同时检索纳入文献的参考文献,并独立对纳入的参考文献进行质量评价和数据提取,采用RevMan5.3软件进行Meta分析.结果 1)最终纳入6篇文献、共518例患者,Jadad量表评分均≥3分;各研究均是随机入组并明确指出组间基线具有可比性;1篇文献使用了盲法.2)大黄附子汤联合西医常规治疗组在胃肠功能评分[MD=-0.35,95％CI(-0.58,-0.12)]、胃肠功能Ⅲ级发生率[OR=0.26,95％CI(0.13,0.55)]、急性生理与慢性健康(APACHEⅡ)评分[MD=-4.23,95％CI(-5.01,-3.44)]方面优于单纯西医治疗组,在28 d病死率方面组间无统计学差异(P＞0.05).结论 大黄附子汤有助于改善脓毒症胃肠功能障碍及病情,未出现明显不良反应.

OBJECTIVE:To evaluate the efficacy of Shenfu decoction (SFD) prepared with a traditional Chinese formula, on sepsis in rats with the condition induced by cecal ligation and puncture (CLP), and to study the possible mechanism underlying its action.METHODS:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups: normal control group (NCG, n = 10), model control group (MCG, n = 15) and Shenfu decoction group (SFDG, n = 15). Sham-operated rats in NCG were served as operation control, while rats in both MCG and SFDG were exposed to CLP, a procedure to develop experimental sepsis. Rats in SFDG were administered with SFD by gavage (3 mg/g of body weight, twice a day) 2 h prior to CLP and directly after successful CLP, while rats in NCG and MCG were gavaged with equivalent volume of sterilized water. Rats in all groups were starved with free access to drink. After 24 h of administration, the mortality of rats in each group was assessed. The indicators of inflammatory response [the peritoneal inflammation by Simon's method Classification as well as serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme linked immunosorbent assay (ELISA)] in survival rats were evaluated. The indicators of gut barrier [The intestinal mucosal injury index, serum concentrations of D-lactic acid and secretory IgA (sIgA) in intestinal mucosa by ELISA, as well as gut microbiota by16S rRNA gene sequencing] in survival rats were evaluated.RESULTS:The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (P < 0.01). The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (χ2 = 6.533, P = 0.011). Compared with the MCG,the peritoneal inflammation as well as serum concentrations of TNF-α and IL-6 decreased significantly in SFDG (all P < 0.01). Compared with the MCG, the IMII, serum concentrations of D-lactic acid, sIgA in intestinal mucosa were alleviated by SFD treatment (all P < 0.01). Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment.CONCLUSION:SFD may play a protective role in sepsis by alleviating sepsis-induced inflammatory response and gut barrier damage in rats.

Objective:To investigate the protective effect of Dahuang Fuzi Decoction（DHFZD）,a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group（NCG,n=10）,model control group（MCG,n=15） and DHFZD-treated group（DHFZDG,n=15）.NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture（CLP）.The DHFZDG rats received DHFZD by gavage（4.5 mg/g of body weight） 2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index（IMII） in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor（TNF）-α,interleukin（IL）-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A（sIgA） in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16 S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-α and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

ETHNOPHARMACOLOGICAL RELEVANCE:Shen-Fu Decoction (SFD), a classic Traditional Chinese paired herb formulation, has been widely used for the treatment of sepsis in China. This study was carried out to assess the effects of SFD in sepsis-induced intestinal permeability and intestinal epithelial tight junction damage in rats with sepsis.MATERIALS AND METHODS:A rat model of sepsis was created by cecal ligation and puncture (CLP). Rats in Sham and CLP + vehicle groups received equal distilled water, while rats in SFD group were treated by gavage of SFD (3 mg/kg, twice a day) for 72h. Mortality, sepsis-induced peritoneal inflammation, intestinal and liver histopathology damage, intestinal permeability (serum FITC-dextran and D-lactate), serum LPS, serum inflammation (PCT, TNF-α, and IL-6), and liver function (AST and ALT) were evaluated. The levels of zonula occluden (ZO-1), Occludin, Claudin-1 were analyzed by Real-time quantitative PCR and Western blotting (WB) respectively. Vasodilator-stimulated phosphoprotein (VASP) and p-VASP in intestinal epithelium were analyzed by WB.RESULTS:Our study showed that SFD markedly reduced the mortality rate of CLP rats, prevented intestine and liver damage, relieved sepsis-induced intestinal permeability and inflammation elevation, ameliorated sepsis-induced impaired intestinal permeability by regulating the expression of ZO-1, Occludin, Claudin-1 and p-VASP.CONCLUSIONS:The herbal formula SFD may be useful for reducing sepsis-induced organic damage and mortality by ameliorating the condition of sepsis-induced intestinal permeability by regulating tight junction proteins and p-VASP.

OBJECTIVE:Besides neurons, activated microglia and astrocytes in the spinal cord dorsal horn (SCDH) contribute to the pathogenesis of chronic pain. Electroacupuncture (EA) has been used widely to treat various chronic pain diseases, however, the underlying mechanisms of EA are still not fully understood.METHODS:Male Sprague-Dawley rats were randomly divided into four groups, including an untreated healthy Control group (n=14), a True-spinal nerve ligation (SNL) group that underwent SNL and remained untreated (n=25), a True-SNL+EA group that underwent SNL followed by EA treatment (n=25), and a Sham-SNL group that underwent sham surgery and remained untreated (n=15). SNL was performed unilaterally at L5 and EA was applied to ST36 and BL60 bilaterally once per day. Paw withdrawal thresholds (PWTs) were measured ipsilaterally at baseline and 1, 3, 7, and 14 days after ligation. Activation of microglia and astrocytes in the SCDH were examined bilaterally by immunofluorescence staining, and concentrations of interleukin-1β (IL-1β) and interleukin (IL-6) were measured in the ipsilateral SCDH by ELISA.RESULTS:SNL significantly decreased PWTs and activated glial cells in the superficial laminae of the ipsilateral SCDH. In rats with SNL, glial fibrillary acidic protein (GFAP) immunoreactivity peaked at 7 days and was maintained until 14 days post-ligation, while anti-integrin alphaM (OX-42) immunoreactivity peaked at 3 days and declined gradually. EA significantly alleviated SNL-induced mechanical allodynia. Furthermore, EA reduced microglial activation (OX-42 positive ratios) in the lumbar SCDH at 3 days post-ligation and suppressed astrocyte activation (GFAP positive ratios) at all time points observed.CONCLUSIONS:EA stimulation alleviates SNL-induced neuropathic pain, at least in part through inhibition of spinal glial activation. Moreover, inhibition of spinal microglia and astrocyte activation may contribute to the immediate effects and maintenance of EA analgesia, respectively.

OBJECTIVE:To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia. METHODS:There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above. RESULTS:SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05). CONCLUSIONS:The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.